Prosthetic valve delivery system with independently-movable capsule portions

ABSTRACT

Prosthetic valves and methods of use of prosthetic valves may be provided. In one implementation, a method of releasing a prosthetic valve from a delivery capsule within a heart may be provided. The delivery capsule may include a distal capsule portion and a proximal capsule portion. The method may include moving the distal capsule portion in a first direction to release ventricular anchoring legs of the prosthetic valve from the delivery capsule and moving the released legs into contact with a native mitral valve. The method may include moving the proximal capsule portion in a second direction to release atrial anchoring arms of the prosthetic valve from the delivery capsule, after contacting the mitral valve with the released legs. The method may include moving the distal capsule portion in the first direction to release an annular valve body of the prosthetic valve from the delivery capsule.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/682,789, filed Aug. 22, 2017, now pending, which is a continuation ofU.S. patent application Ser. No. 15/541,783, filed Jul. 6, 2017, whichissued as U.S. Pat. No. 9,974,651 on May 22, 2018, which is a U.S.national stage entry under 35 U.S.C. § 371 of International ApplicationNo. PCT/IL2016/050125, filed Feb. 3, 2016, which claims priority fromU.S. Provisional Patent Application No. 62/112,343, filed Feb. 5, 2015,all of which are hereby incorporated by reference in their entirety.This application also claims priority from U.S. Provisional PatentApplication No. 62/560,384, filed Sep. 19, 2017, which is herebyincorporated by reference in its entirety.

FIELD OF THE INVENTION

Some embodiments of the present disclosure relate in general to valvereplacement. More specifically, some embodiments of the presentdisclosure relate to prosthetic valves for replacement of a cardiacvalve.

BACKGROUND

Ischemic heart disease causes regurgitation of a heart valve by thecombination of ischemic dysfunction of the papillary muscles, and thedilatation of the ventricle that is present in ischemic heart disease,with the subsequent displacement of the papillary muscles and thedilatation of the valve annulus.

Dilatation of the annulus of the valve prevents the valve leaflets fromfully coapting when the valve is closed. Regurgitation of blood from theventricle into the atrium results in increased total stroke volume anddecreased cardiac output, and ultimate weakening of the ventriclesecondary to a volume overload and a pressure overload of the atrium.

SUMMARY OF THE INVENTION

For some embodiments of the present disclosure, an implant is providedhaving a tubular portion, an upstream support portion and one or moreflanges. The implant is percutaneously deliverable to a native heartvalve in a compressed state, and is expandable at the native valve. Theimplant and its delivery system facilitate causing the upstream supportportion and the flanges to protrude radially outward from the tubularportion without expanding the tubular portion. Expansion of the tubularportion brings the upstream support portion and the flanges closertogether, for securing the implant at the native valve by sandwichingtissue of the native valve between the upstream support portion and theflanges.

In accordance with an embodiment of the present disclosure, an apparatusis provided for use with a native valve that is disposed between anatrium and a ventricle of a heart of a subject, the apparatus includinga valve frame, including a tubular portion that circumscribes alongitudinal axis of the valve frame so as to define a lumen along theaxis, the tubular portion defining a plurality of valve-frame couplingelements disposed circumferentially around the longitudinal axis; aplurality of prosthetic leaflets, coupled to the frame, disposed withinthe lumen, and arranged to provide unidirectional flow of blood from anupstream end of the lumen to a downstream end of the lumen; an outerframe including a ring defined by a pattern of alternating peaks andtroughs, the peaks being longitudinally closer to the upstream end thanto the downstream end, and the troughs being longitudinally closer tothe downstream end than to the upstream end, and the pattern of the ringhaving an amplitude longitudinally between the peaks and the troughs,including a plurality of legs, each of the legs coupled to the ring at arespective trough, and shaped to define a plurality of outer-framecoupling elements, each of the outer-frame coupling elements (i) coupledto the ring at a respective peak, and (ii) fixed with respect to arespective valve-frame coupling element, and the tubular portion has (i)a compressed state in which the tubular portion has a compresseddiameter, and (ii) an expanded state in which the tubular portion has anexpanded diameter that is greater than the compressed diameter, and thefixation of the outer-frame coupling elements to the valve-framecoupling elements is such that compression of the tubular portion fromthe expanded state toward the compressed state such that the valve-framecoupling elements pull the outer-frame coupling elements radially inward(i) reduces a circumferential distance between each of the outer-framecoupling elements and its adjacent outer-frame coupling elements, and(ii) increases the amplitude of the pattern of the ring.

In an embodiment, the ring circumscribes the tubular portion.

In an embodiment, the valve-frame coupling elements are disposedcircumferentially around the longitudinal axis between the upstream endand the downstream end but not at the upstream end nor at the downstreamend.

In an embodiment, the upstream support portion includes one or morefabric pockets disposed circumferentially, each pocket of the one ormore pockets having an opening that faces a downstream direction.

In an embodiment, the outer frame is coupled to the valve frame only viathe fixation of the outer-frame coupling elements to the respectivevalve-frame coupling elements.

In an embodiment, the apparatus further includes an upstream supportportion that includes a plurality of arms that extend radially from thetubular portion, and the upstream support portion has (i) aconstrained-arm state, and (ii) a released-arm state in which the armsextend radially outward from the tubular portion, each leg has atissue-engaging flange that has (i) a constrained-flange state, and (ii)a released-flange state in which the flange extends radially outwardfrom the tubular portion, and the apparatus has an intermediate state inwhich (i) the tubular portion is in its compressed state, (ii) theupstream support portion is in its released-arm state, and (iii) thelegs are in their released-flange state.

In an embodiment, the apparatus includes an implant that includes thevalve frame, the leaflets, and the outer frame, and the apparatusfurther includes a tool including a delivery capsule dimensioned (i) tohouse and retain the implant in a compressed state of the implant inwhich (a) the tubular portion is in its compressed state, (b) theupstream support portion is in its constrained-arm state, and (c) thelegs are in their constrained-flange state, and (ii) to be advancedpercutaneously to the heart of the subject while the implant is housedand in its compressed state, and operable from outside the subject totransition the implant from its compressed state into the intermediatestate while retaining the tubular portion in its compressed state, andsubsequently, expand the tubular portion toward its expanded state.

In an embodiment, the tool is operable from outside the subject totransition the implant from its compressed state into the intermediatestate by (i) releasing the legs into their released-flange state, whileretaining the tubular portion in its compressed state, and (ii)subsequently, releasing the upstream support portion into itsreleased-arm state, while retaining the tubular portion in itscompressed state.

In an embodiment, the tool is operable from outside the subject totransition the implant from its compressed state into the intermediatestate by (i) releasing the upstream support portion into itsreleased-arm state, while retaining the tubular portion in itscompressed state, and (ii) subsequently, releasing the legs into theirreleased-flange state, while retaining the tubular portion in itscompressed state.

In an embodiment, the fixation of the outer-frame coupling elements tothe valve-frame coupling elements is such that, when the apparatus is inits intermediate state, expansion of the tubular portion from itscompressed state toward its expanded state moves the flangeslongitudinally away from the valve-frame coupling elements.

In an embodiment, the fixation of the outer-frame coupling elements tothe valve-frame coupling elements is such that, when the apparatus is inits intermediate state, expansion of the tubular portion from acompressed state toward an expanded state reduces the amplitude of thepattern of the ring and passes the flanges between the arms.

In an embodiment, the upstream support portion further includes acovering that covers the arms to form an annular shape in thereleased-arm state, and, when the apparatus is in its intermediatestate, expansion of the tubular portion from its compressed state towardits expanded state presses the flanges onto the covering.

In an embodiment, in the compressed state of the tubular portion, adownstream end of each leg of the tubular portion is longitudinallycloser than the valve-frame coupling elements to the downstream end, andthe flange of each leg is disposed longitudinally closer than thevalve-frame coupling elements to the upstream end.

In an embodiment, in the expanded state of the tubular portion, thedownstream end of each leg is longitudinally closer than the valve-framecoupling elements to the downstream end, and the flange of each leg isdisposed longitudinally closer than the valve-frame coupling elements tothe upstream end.

In accordance with an embodiment of the present disclosure, an apparatusfor use with a native valve of a heart of a subject is provided, theapparatus having an implant that includes a valve frame that includes atubular portion that circumscribes a longitudinal axis of the valveframe so as to define a lumen along the axis, the tubular portion havingan upstream end, a downstream end, a longitudinal length therebetween,and a diameter transverse to the longitudinal axis; a valve member,coupled to the tubular portion, disposed within the lumen, and arrangedto provide unidirectional upstream-to-downstream flow of blood throughthe lumen; an upstream support portion, coupled to the tubular portion;and an outer frame, coupled to the tubular portion, and including atissue-engaging flange, and the implant has a first state and a secondstate, in both the first state and the second state, (i) the upstreamsupport portion extends radially outward from the tubular portion, and(ii) the tissue-engaging flange extends radially outward from thetubular portion, and the tubular portion, the upstream support portion,and the outer frame are arranged such that transitioning of the implantfrom the first state toward the second state increases the diameter ofthe tubular portion by a diameter-increase amount, decreases the lengthof the tubular portion by a length-decrease amount, and moves the flangea longitudinal distance toward or toward-and-beyond the upstream supportportion, the distance being greater than the length-decrease amount.

In an embodiment of the present disclosure, the tubular portion, theupstream support portion, and the outer frame may be arranged such thatthe longitudinal distance is more than 20 percent greater than thelength-decrease amount.

In an embodiment, the tubular portion, the upstream support portion, andthe outer frame may be arranged such that the longitudinal distance ismore than 30 percent greater than the length-decrease amount.

In an embodiment, the tubular portion, the upstream support portion, andthe outer frame may be arranged such that the longitudinal distance ismore than 40 percent greater than the length-decrease amount.

In accordance with an embodiment of the present disclosure, an apparatusfor use with a native valve that is disposed between an atrium and aventricle of a heart of a subject is provided, the apparatus including avalve frame, including a tubular portion that circumscribes alongitudinal axis of the valve frame so as to define a lumen along theaxis; a plurality of prosthetic leaflets, coupled to the frame, disposedwithin the lumen, and arranged to provide unidirectional flow of bloodfrom an upstream end of the lumen to a downstream end of the lumen; anouter frame, including a ring defined by a pattern of alternating peaksand troughs the peaks being longitudinally closer than the troughs tothe upstream end, the peaks being fixed to respective sites of thetubular portion at respective coupling points disposed circumferentiallyaround the longitudinal axis, and the pattern of the ring having anamplitude longitudinally between the peaks and the troughs; and aplurality of legs, each of the legs coupled to the ring at a respectivetrough, and the tubular portion has (i) a compressed state in which thetubular portion has a compressed diameter, and (ii) an expanded state inwhich the tubular portion has an expanded diameter that is greater thanthe compressed diameter, and the fixation of the peaks to the respectivesites of the tubular portion is such that compression of the tubularportion from the expanded state toward the compressed state such thatthe respective sites of the tubular portion pull the peaks radiallyinward via radially-inward tension on the coupling points (i) reduces acircumferential distance between each of the coupling points and itsadjacent coupling points, and (ii) increases the amplitude of thepattern of the ring.

In an embodiment, the outer frame may be coupled to the valve frame onlyvia the fixation of the peaks to the respective sites of the tubularportion at the respective coupling points.

In accordance with an embodiment of the present disclosure, an apparatusfor use with a native valve that is disposed between an atrium and aventricle of a heart of a subject is provided, the apparatus including avalve frame, including a tubular portion that circumscribes alongitudinal axis of the valve frame so as to define a lumen along theaxis, the valve frame defining a plurality of valve-frame couplingelements disposed circumferentially around the longitudinal axis; aplurality of prosthetic leaflets, coupled to the frame, disposed withinthe lumen, and arranged to provide unidirectional flow of blood from anupstream end of the lumen to a downstream end of the lumen; an outerframe including a ring defined by a pattern of alternating peaks andtroughs, the peaks being longitudinally closer to the upstream end thanto the downstream end, and the troughs being longitudinally closer tothe downstream end than to the upstream end, and the pattern of the ringhaving an amplitude longitudinally between the peaks and the troughs,including a plurality of legs, each of the legs coupled to the ring at arespective trough, and shaped to define a plurality of outer-framecoupling elements, each of the outer-frame coupling elements (i) coupledto the ring at a respective peak, and (ii) fixed with respect to arespective valve-frame coupling element, and the tubular portion has (i)a compressed state in which the tubular portion has a compresseddiameter, and (ii) an expanded state in which the tubular portion has anexpanded diameter that is greater than the compressed diameter, and thefixation of the outer-frame coupling elements with respect to thevalve-frame coupling elements is such that compression of the tubularportion from the expanded state toward the compressed state (i) pullsthe outer-frame coupling elements radially inward via radially-inwardpulling of the valve-frame coupling elements on the outer-frame couplingelements, (ii) reduces a circumferential distance between each of theouter-frame coupling elements and its adjacent outer-frame couplingelements, and (iii) increases the amplitude of the pattern of the ring,without increasing a radial gap between the valve frame and the ring bymore than 1.5 mm.

In an embodiment, the outer frame may be coupled to the valve frame onlyvia the fixation of the outer-frame coupling elements to the respectivevalve-frame coupling elements.

There is further provided, in accordance with an embodiment of thepresent disclosure, an apparatus for use with a native valve that isdisposed between an atrium and a ventricle of a heart of a subject isprovided, the apparatus including a valve frame, including a tubularportion that circumscribes a longitudinal axis of the valve frame so asto define a lumen along the axis; a plurality of prosthetic leaflets,coupled to the frame, disposed within the lumen, and arranged to provideunidirectional flow of blood from an upstream end of the lumen to adownstream end of the lumen; an outer frame, including a ring defined bya pattern of alternating peaks and troughs the peaks beinglongitudinally closer than the troughs to the upstream end, the peaksbeing fixed to respective sites of the tubular portion at respectivecoupling points disposed circumferentially around the longitudinal axis,and the pattern of the ring having an amplitude longitudinally betweenthe peaks and the troughs; and a plurality of legs, each of the legscoupled to the ring at a respective trough, and the tubular portion has(i) a compressed state in which the tubular portion has a compresseddiameter, and (ii) an expanded state in which the tubular portion has anexpanded diameter that is greater than the compressed diameter, and thefixation of the peaks to the respective sites of the tubular portion issuch that compression of the tubular portion from the expanded statetoward the compressed state (i) pulls the peaks radially inward viaradially-inward pulling of the respective sites of the tubular portionon the peaks, (ii) reduces a circumferential distance between each ofthe coupling points and its adjacent coupling points, and (iii)increases the amplitude of the pattern of the ring, without increasing aradial gap between the valve frame and the ring by more than 1.5 mm.

In an embodiment, the outer frame may be coupled to the valve frame onlyvia the fixation of the peaks to the respective sites of the tubularportion at the respective coupling points.

In accordance with an embodiment of the present disclosure, an apparatusfor use with a native valve disposed between an atrium and a ventricleof a heart of a subject is provided, the apparatus including a valveframe, including a tubular portion that circumscribes a longitudinalaxis of the valve frame so as to define a lumen along the axis, thetubular portion having an upstream end, a downstream end, and defining aplurality of valve-frame coupling elements disposed circumferentiallyaround the longitudinal axis between the upstream end and the downstreamend but not at the upstream end nor at the downstream end; a pluralityof prosthetic leaflets, disposed within the lumen, and arranged toprovide unidirectional flow of blood through the lumen; an outer frameincluding a ring defined by a pattern of alternating peaks and troughs,the peaks being longitudinally closer to the upstream end than to thedownstream end, and the troughs being longitudinally closer to thedownstream end than to the upstream end, including a plurality of legs,each of the legs coupled to the ring at a respective trough, and shapedto define a plurality of outer-frame coupling elements, each of theouter-frame coupling elements (i) coupled to the ring at a respectivepeak, and (ii) fixed with respect to a respective valve-frame couplingelement at a respective coupling point, and the tubular portion has (i)a compressed state in which the tubular portion has a compresseddiameter, and (ii) an expanded state in which the tubular portion has anexpanded diameter that is greater than the compressed diameter, andexpansion of the tubular portion from the compressed state toward theexpanded state (i) increases a circumferential distance between each ofthe outer-frame coupling elements and its adjacent outer-frame couplingelements, and (ii) moves the plurality of legs in a longitudinallyupstream direction with respect to the tubular portion.

In an embodiment, the outer frame may be coupled to the valve frame onlyvia the fixation of the outer-frame coupling elements to the respectivevalve-frame coupling elements.

In accordance with an embodiment of the present disclosure, an apparatusfor use with a native valve disposed between an atrium and a ventricleof a heart of a subject is provided, the apparatus including a valveframe, including a tubular portion that circumscribes a longitudinalaxis of the valve frame so as to define a lumen along the axis, thetubular portion having an upstream end and a downstream end; a pluralityof prosthetic leaflets, disposed within the lumen, and arranged toprovide unidirectional flow of blood through the lumen; an outer frame,including a ring defined by a pattern of alternating peaks and troughsthe peaks being longitudinally closer than the troughs to the upstreamend, the peaks being fixed to respective sites of the tubular portion atrespective coupling points disposed circumferentially around thelongitudinal axis between the upstream end and the downstream end butnot at the upstream end nor the downstream end; and a plurality of legs,each of the legs coupled to the ring at a respective trough, and thetubular portion has (i) a compressed state in which the tubular portionhas a compressed diameter, and (ii) an expanded state in which thetubular portion has an expanded diameter that is greater than thecompressed diameter, and expansion of the tubular portion from thecompressed state toward the expanded state (i) increases acircumferential distance between each of the coupling points and itsadjacent coupling points, and (ii) moves the plurality of legs in alongitudinally upstream direction with respect to the tubular portion.

In an embodiment, the outer frame may be coupled to the valve frame onlyvia the fixation of the peaks to the respective sites of the tubularportion at the respective coupling points.

In accordance with an embodiment of the present disclosure, an apparatusfor use with a native valve of a heart of a subject is provided, theapparatus including a frame assembly, having an upstream end and adownstream end, and a central longitudinal axis therebetween, andincluding a valve frame, including a tubular portion having an upstreamend and a downstream end, and shaped to define a lumen therebetween, andan upstream support portion, extending from the upstream end of thetubular portion; and at least one leg, coupled to the valve frame at acoupling point, and having a tissue-engaging flange; and a valve memberdisposed within the lumen, and configured to facilitate one-way liquidflow through the lumen from the upstream end of the tubular portion tothe downstream end of the tubular portion, and the frame assembly has acompressed state, for percutaneous delivery to the heart, in which thetubular portion has a compressed diameter, is biased to assume anexpanded state in which the tubular portion has an expanded diameterthat is greater than the compressed diameter, and is configured suchthat increasing the diameter of the tubular portion toward the expandeddiameter causes longitudinal movement of the upstream support portiontoward the coupling point, and of the tissue-engaging flange away fromthe coupling point.

In an embodiment the apparatus includes an implant that includes theframe assembly and the valve member, and the apparatus further includesa tool including a delivery capsule dimensioned (i) to house and retainthe implant in the compressed state, and (ii) to be advancedpercutaneously to the heart of the subject while the implant is housedand in the compressed state, and operable from outside the subject tofacilitate an increase of the diameter of the tubular portion from thecompressed diameter toward the expanded diameter such that the increaseof the diameter actuates longitudinal movement of the upstream supportportion toward the coupling point, and of the tissue-engaging flangeaway from the coupling point.

In an embodiment, the frame assembly may be configured such thatincreasing the diameter of the tubular portion by expanding the frameassembly toward the expanded state causes longitudinal movement of theupstream end of the tubular portion toward the coupling point.

In an embodiment, the coupling point is disposed closer to thedownstream end of the frame assembly than are either the tissue-engagingflange or the upstream support portion.

In an embodiment, in the expanded state of the frame assembly, the legextends away from the central longitudinal axis.

In an embodiment, the expanded state of the frame assembly may be afully-expanded state of the frame assembly, the leg is expandable intoan expanded state of the leg, independently of increasing the diameterof the tubular portion, and in the expanded state of the leg, the legextends away from the central longitudinal axis.

In an embodiment, in the expanded state of the frame assembly, the legextends away from the central longitudinal axis, and in the compressedstate of the frame assembly, the leg is generally parallel with thecentral longitudinal axis.

In an embodiment, the frame assembly may be configured such that thelongitudinal movement of the tissue-engaging flange away from thecoupling point is a translational movement of the tissue-engaging flangethat does not include rotation of the tissue-engaging flange.

In an embodiment, the frame assembly may be configured such thatincreasing the diameter of the tubular portion by expanding the frameassembly toward the expanded state causes 1-20 mm of longitudinalmovement of the tissue-engaging flange away from the coupling point.

In an embodiment, the frame assembly may be configured such thatincreasing the diameter of the tubular portion by expanding the frameassembly toward the expanded state causes 1-20 mm of longitudinalmovement of the upstream support portion toward the coupling point.

In an embodiment, the frame assembly may be configured such thatincreasing the diameter of the tubular portion by expanding the frameassembly toward the expanded state reduces a distance between theupstream support portion and the tissue-engaging flange by 5-30 mm.

In an embodiment, the frame assembly may be configured such thatincreasing the diameter of the tubular portion by expanding the frameassembly toward the expanded state moves the tissue-engaging flangelongitudinally past the upstream support portion.

In an embodiment, the tubular portion may be defined by a plurality ofcells of the valve frame, and increasing the diameter of the tubularportion by expanding the frame assembly toward the expanded stateincludes (i) increasing a width, orthogonal to the longitudinal axis ofthe frame assembly, of each cell, and (ii) reducing a height, parallelwith the longitudinal axis of the frame assembly, of each cell, andcauses longitudinal movement of the upstream support portion toward thecoupling point by reducing a height, parallel with the longitudinal axisof the frame assembly, of the tubular portion, by reducing the height ofeach cell.

In an embodiment, the leg is disposed on an outside of the tubularportion.

In an embodiment, the at least one leg includes a plurality of legs, thecoupling point includes a plurality of coupling points, and the frameassembly includes a leg frame that circumscribes the tubular portion,includes the plurality of legs, and is coupled to the valve frame at theplurality of coupling points, such that the plurality of legs isdistributed circumferentially around the tubular portion.

In an embodiment, the plurality of coupling points is disposedcircumferentially around the frame assembly on a transverse plane thatis orthogonal to the longitudinal axis of the frame assembly.

In an embodiment, the plurality of legs may be coupled to the valveframe via a plurality of struts, each strut having a first end that iscoupled to a leg of the plurality of legs, and a second end that iscoupled to a coupling point of the plurality of coupling points, in thecompressed state of the frame assembly, being disposed at a first anglein which the first end is disposed closer to the downstream end of theframe assembly than is the second end, and being deflectable withrespect to the coupling point of the plurality of coupling points, suchthat increasing the diameter of the tubular portion by expanding theframe assembly toward the expanded state causes the strut to deflect toa second angle in which the first end is disposed further from thedownstream end of the frame assembly than is the first end in thecompressed state of the frame assembly.

In an embodiment, the leg frame may be structured such that each leg ofthe plurality of legs is coupled to two struts of the plurality ofstruts, and two struts of the plurality of struts are coupled to eachcoupling point of the plurality of coupling points.

In an embodiment, the leg may be coupled to the valve frame via a strut,the strut having a first end that is coupled to the leg, and a secondend that is coupled to the coupling point, in the compressed state ofthe frame assembly, being disposed at a first angle in which the firstend is disposed closer to the downstream end of the frame assembly thanis the second end, and being deflectable with respect to the couplingpoint, such that increasing the diameter of the tubular portion byexpanding the frame assembly toward the expanded state causes the strutto deflect to a second angle in which the first end is disposed furtherfrom the downstream end of the frame assembly than is the first end inthe compressed state of the frame assembly.

In an embodiment, the at least one leg includes at least a first leg anda second leg.

In an embodiment, the first leg and the second leg are both coupled tothe valve frame at the coupling point.

In an embodiment, the first leg may be coupled to the coupling point viaa respective first strut, and the second leg is coupled to the couplingpoint via a respective second strut.

In an embodiment, the first and second legs, the first and secondstruts, and the coupling point are arranged such that, in the expandedstate of the frame assembly the coupling point is disposed,circumferentially with respect to the tubular portion, between the firststrut and the second strut, the first strut is disposed,circumferentially with respect to the tubular portion, between thecoupling point and the first leg, and the second strut is disposed,circumferentially with respect to the tubular portion, between thecoupling point and the second leg.

In an embodiment, the coupling point includes at least a first couplingpoint and a second coupling point.

In an embodiment, the leg is coupled to the valve frame at the firstcoupling point and at the second coupling point.

In an embodiment, the leg may be coupled to the first coupling point viaa respective first strut, and to the second coupling point via arespective second strut.

In an embodiment, the first and second legs, the first and secondstruts, and the coupling point are arranged such that, in the expandedstate of the frame assembly the leg is disposed, circumferentially withrespect to the tubular portion, between the first strut and the secondstrut, the first strut is disposed, circumferentially with respect tothe tubular portion, between the leg and the first coupling point, andthe second strut is disposed, circumferentially with respect to thetubular portion, between the leg and the second coupling point.

In an embodiment, in the expanded state of the frame assembly, theupstream support portion extends radially outward from the tubularportion.

In an embodiment, the expanded state of the frame assembly is afully-expanded state of the frame assembly, the upstream support portionis expandable into an expanded state of the upstream support portion,independently of increasing the diameter of the tubular portion, and inthe expanded state of the upstream support portion, the upstream supportportion extends radially outward from the tubular portion.

In an embodiment, in the compressed state of the frame assembly, theupstream support portion is generally tubular, collinear with thetubular portion, and disposed around the central longitudinal axis.

In an embodiment, in the expanded state of the frame assembly, an innerregion of the upstream support portion extends radially outward from thetubular portion at a first angle with respect to the tubular portion,and an outer region of the upstream support portion extends, from theinner region of the upstream support portion, further radially outwardfrom the tubular portion at a second angle with respect to the tubularportion, the second angle being smaller than the first angle.

In accordance with an embodiment of the present disclosure, an apparatusfor use with a native valve of a heart of a subject is provided, theapparatus including a frame assembly, having an upstream end and adownstream end, and a central longitudinal axis therebetween, andincluding a valve frame, including a tubular portion having an upstreamend and a downstream end, and shaped to define a lumen therebetween, andan upstream support portion, extending from the upstream end of thetubular portion; and at least one leg, coupled to the valve frame at acoupling point, and having a tissue-engaging flange; and a valve memberdisposed within the lumen, and configured to facilitate one-way liquidflow through the lumen from the upstream end of the tubular portion tothe downstream end of the tubular portion, and the frame assembly has acompressed state, for percutaneous delivery to the heart, in which thetubular portion has a compressed diameter, is biased to assume anexpanded state in which the tubular portion has an expanded diameterthat is greater than the compressed diameter, and is configured suchthat reducing the diameter of the tubular portion toward the compresseddiameter causes longitudinal movement of the upstream support portionaway from the coupling point, and of the tissue-engaging flange towardthe coupling point.

In accordance with an embodiment of the present disclosure, an apparatusfor use with a native valve of a heart of a subject is provided, theapparatus including a frame assembly, having an upstream end and adownstream end, and a central longitudinal axis therebetween, includinga valve frame, including a tubular portion having an upstream end and adownstream end, and shaped to define a lumen therebetween, and anupstream support portion, extending from the upstream end of the tubularportion; and at least one leg, coupled to the valve frame at a couplingpoint, and having a tissue-engaging flange; and a valve member disposedwithin the lumen, and configured to facilitate one-way liquid flowthrough the lumen from the upstream end of the tubular portion to thedownstream end of the tubular portion, and the frame assembly has acompressed state, for percutaneous delivery to the heart, isintracorporeally expandable into an expanded state in which a diameterof the tubular portion is greater than in the compressed state, and isconfigured such that increasing the diameter of the tubular portion byexpanding the frame assembly toward the expanded state causeslongitudinal movement of the tissue-engaging flange away from thecoupling point.

In accordance with an embodiment of the present disclosure, an apparatusfor use with a native valve of a heart of a subject is provided, theapparatus including a frame assembly, having an upstream end and adownstream end, and a central longitudinal axis therebetween, andincluding an inner frame including an inner-frame tubular portion thatcircumscribes the central longitudinal axis, has an upstream end and adownstream end, and defines a channel therebetween, the inner framedefining a plurality of inner-frame couplings disposed circumferentiallyat a longitudinal location of the inner frame, an outer frame includingan outer-frame tubular portion that coaxially circumscribes at least aportion of the inner-frame tubular portion, the outer frame defining aplurality of outer-frame couplings disposed circumferentially at alongitudinal location of the outer frame, and a plurality of connectors,each connector connecting a respective inner-frame coupling to arespective outer-frame coupling; a liner, disposed over at least part ofthe inner-frame tubular portion; and a plurality of prosthetic leaflets,coupled to the inner-frame tubular portion and disposed within thechannel, and the frame assembly (i) is compressible by aradially-compressive force into a compressed state in which the innerframe is in a compressed state thereof and the outer frame is in acompressed state thereof, (ii) is configured, upon removal of theradially-compressive force, to automatically expand into an expandedstate thereof in which the inner frame is in an expanded state thereofand the outer frame is in an expanded state thereof, in the expandedstate of the frame assembly, the prosthetic leaflets are configured tofacilitate one-way fluid flow, in a downstream direction, through thechannel, and the connection of the inner-frame couplings to therespective outer-frame couplings is such that expansion of the frameassembly from the compressed state to the expanded state causes theinner-frame tubular portion to slide longitudinally in a downstreamdirection with respect to the outer-frame tubular portion.

In accordance with an embodiment of the present disclosure, an apparatusfor use with a native valve disposed between an atrium and a ventricleof a heart of a subject is provided, the apparatus including a tubularportion, having an upstream portion that includes an upstream end, and adownstream portion that includes a downstream end, and shaped to definea lumen between the upstream portion and the downstream portion; aplurality of prosthetic leaflets, disposed within the lumen, andarranged to provide unidirectional flow of blood from the upstreamportion to the downstream portion; an annular upstream support portionhaving an inner portion that extends radially outward from the upstreamportion, and including one or more fabric pockets disposedcircumferentially around the inner portion, each pocket of the one ormore pockets having an opening that faces a downstream direction.

In an embodiment, the upstream support portion includes (i) a pluralityof arms that extend radially outward from the tubular portion, and (ii)a covering, disposed over the plurality of arms, each arm has (i) aradially-inner part at the inner portion of the upstream supportportion, and (ii) a radially-outer part at the outer portion of theupstream support portion, at the inner portion of the upstream supportportion, the covering is closely-fitted between the radially-inner partsof the arms, and at the outer portion of the upstream support portion,the pockets are formed by the covering being loosely-fitted between theradially-outer parts of the arms.

In an embodiment, the upstream support portion includes (i) a pluralityof arms that extend radially outward from the tubular portion, and (ii)a covering, disposed over the plurality of arms, each arm has (i) aradially-inner part at the inner portion of the upstream supportportion, and (ii) a radially-outer part at the outer portion of theupstream support portion, the radially-outer part being more flexiblethan the radially-inner part.

In an embodiment, the upstream support portion includes (i) a pluralityof arms that extend radially outward from the tubular portion, and (ii)a covering, disposed over the plurality of arms, each arm has (i) aradially-inner part at the inner portion of the upstream supportportion, and (ii) a radially-outer part at the outer portion of theupstream support portion, at the outer portion of the upstream supportportion, the pockets are formed by each arm curving to form a hookshape.

In an embodiment, each pocket may be shaped and arranged to billow inresponse to perivalvular flow of blood in an upstream direction.

In an embodiment, the apparatus may be configured to be transluminallydelivered to the heart and implanted at the native valve by expansion ofthe apparatus, such that the upstream support portion is disposed in theatrium and the tubular portion extends from the upstream support portioninto the ventricle, and each pocket is shaped and arranged such thatperivalvular flow of blood in an upstream direction presses the pocketagainst tissue of the atrium.

In accordance with an embodiment of the present disclosure, an apparatusis provided including a plurality of prosthetic valve leaflets; and aframe assembly, including a tubular portion defined by a repeatingpattern of cells, the tubular portion extending circumferentially arounda longitudinal axis so as to define a longitudinal lumen, the prostheticvalve leaflets coupled to the inner frame and disposed within the lumen;an outer frame, including a plurality of legs, distributedcircumferentially around the tubular portion, each leg having atissue-engaging flange; an upstream support portion that includes aplurality of arms that extend radially outward from the tubular portion;and a plurality of appendages, each having a first end that defines acoupling element via which the tubular portion is coupled to the outerframe, and a second end; and the frame assembly defines a plurality ofhubs, distributed circumferentially around the longitudinal axis on aplane that is transverse to the longitudinal axis, each hub defined byconvergence and connection of, (i) two adjacent cells of the tubularportion, (ii) an arm of the plurality of arms, and (iii) an appendage ofthe plurality of appendages.

In an embodiment, each hub has six radiating spokes, two of the sixspokes being part of a first cell of the two adjacent cells, two of thesix spokes being part of a second cell of the two adjacent cells, one ofthe six spokes being the arm, and one of the six spokes being the secondend of the appendage.

In an embodiment, the appendages are in-plane with the tubular portion.

In an embodiment, the appendages are in-plane with the outer frame.

In accordance with an embodiment of the present disclosure, a method foruse with a native valve of a heart of a subject is provided, the methodincluding percutaneously advancing to heart, an implant including avalve frame, a valve member disposed within a lumen defined by the valveframe, and at least one leg, coupled to the valve frame at a couplingpoint, and having an upstream end, a downstream end, and a centrallongitudinal axis therebetween; positioning the implant within the heartsuch that a tissue-engaging flange of the leg is disposed downstream ofthe valve, and thereafter causing the flange to protrude radiallyoutward from the axis; subsequently, while an upstream support portionof the valve frame is disposed upstream of the valve, causing theupstream support portion to protrude radially outward from the axis,such that tissue of the valve is disposed between the upstream supportportion and the flange; and subsequently, sandwiching the tissue betweenthe upstream support portion and the flange by reducing a distancebetween the upstream support portion and the flange by causinglongitudinal movement (i) of the upstream support portion toward thecoupling point, and (ii) of the tissue-engaging flange away from thecoupling point.

In an embodiment, causing the longitudinal movement (i) of the upstreamsupport portion toward the coupling point, and (ii) of thetissue-engaging flange away from the coupling point, includes causingthe longitudinal movement by increasing a diameter of the lumen.

In accordance with an embodiment of the present disclosure, a method foruse with a native valve of a heart of a subject is provided, the methodincluding percutaneously advancing to heart, an implant including avalve frame, a valve member disposed within a lumen defined by the valveframe, and at least one leg, coupled to the valve frame at a couplingpoint, and having an upstream end, a downstream end, and a centrallongitudinal axis therebetween; positioning the implant within the heartsuch that an upstream support portion of the valve frame is disposedupstream of the valve, and thereafter causing the upstream supportportion to protrude radially outward from the axis; subsequently, whilea tissue-engaging flange of the leg is disposed downstream of the valve,causing the tissue-engaging flange to protrude radially outward from theaxis, such that tissue of the valve is disposed between the upstreamsupport portion and the flange; and subsequently, sandwiching the tissuebetween the upstream support portion and the flange by reducing adistance between the upstream support portion and the flange by causinglongitudinal movement (i) of the upstream support portion toward thecoupling point, and (ii) of the tissue-engaging flange away from thecoupling point.

In an embodiment, causing the longitudinal movement (i) of the upstreamsupport portion toward the coupling point, and (ii) of thetissue-engaging flange away from the coupling point, includes causingthe longitudinal movement by increasing a diameter of the lumen.

In accordance with an embodiment of the present disclosure, a method foruse with a native valve of a heart of a subject is provided, the methodincluding percutaneously advancing an implant to the heart, the implanthaving an upstream end, a downstream end, and a central longitudinalaxis therebetween, and including a tubular portion, an upstream supportportion, and a plurality of tissue-engaging flanges; positioning theimplant within the heart such that the upstream support portion isdisposed upstream of the valve, positioning the implant within the heartsuch that the tissue-engaging flanges are disposed downstream of thevalve, without increasing a diameter of the tubular portion causing theupstream support portion to extend radially outward from the axis so asto have a first support-portion span, and causing the flanges to extendradially outward from the axis so as to have a first flange span; andsubsequently, causing the upstream support portion and the flanges movetoward each other by at least 5 mm by increasing a diameter of thetubular portion such that the upstream support portion extends radiallyoutward so as to have a second support-portion span, the firstsupport-portion span being at least 40 percent as great as the secondsupport-portion span, and the flanges extend radially outward so as tohave a second flange span, the first flange span being at least 30percent as great as the second flange span.

There is further provided, in accordance with an embodiment of thepresent disclosure, a method for use with a native valve of a heart of asubject, the method including percutaneously advancing an implant to theheart, the implant having an upstream end, a downstream end, and acentral longitudinal axis therebetween, and including a tubular portion,an upstream support portion, and a plurality of tissue-engaging flanges;positioning the implant within the heart such that the upstream supportportion is disposed upstream of the valve, positioning the implantwithin the heart such that the tissue-engaging flanges are disposeddownstream of the valve, without increasing a diameter of the tubularportion causing the upstream support portion to extend radially outwardfrom the axis, and causing the flanges to extend radially outward fromthe axis so as to have a first flange span; and subsequently, byincreasing a diameter of the tubular portion causing the upstreamsupport portion and the flanges move toward each other by at least 5 mm,causing the upstream support portion to move further radially outwardfrom the axis, and causing each flange of the plurality of flanges totranslate radially outward so as to have a second flange span that isgreater than the first flange span.

The present disclosure will be more fully understood from the followingdetailed description of embodiments thereof, taken together with thedrawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-B and 2A-E are schematic illustrations of an implant for usewith a native valve of a heart of a subject, in accordance with someembodiments of the disclosure;

FIGS. 3A-C are schematic illustrations that show structural changes in aframe assembly during transitioning of the assembly between itscompressed and expanded states, in accordance with some embodiments ofthe disclosure;

FIGS. 4A-F are schematic illustrations of implantation of the implant atthe native valve, in accordance with some embodiments of the disclosure;

FIG. 5 is a schematic illustration of a step in the implantation of theimplant, in accordance with some embodiments of the disclosure;

FIG. 6 is a schematic illustration of the implant, in accordance withsome embodiments of the disclosure;

FIGS. 7A-B and 8A-B are schematic illustrations of frame assemblies ofrespective implants, in accordance with some embodiments of thedisclosure; and

FIGS. 9A-C are schematic illustrations of an implant including a frameassembly, in accordance with some embodiments of the disclosure.

DETAILED DESCRIPTION OF EMBODIMENTS

Reference is made to FIGS. 1A-B and 2A-E, which are schematicillustrations of an implant 20 (alternatively, “prosthetic valve 20”)for use with a native valve of a heart of a subject, in accordance withsome embodiments of the disclosure. Prosthetic valve 20 includes a frameassembly 22 that has an upstream end 24, a downstream end 26, and acentral longitudinal axis ax1 therebetween. Frame assembly 22 includes avalve frame 30 that includes a tubular portion 32 (alternatively, “valveframe tubular portion 32”) that has an upstream end 34 and a downstreamend 36, and is shaped to define a lumen 38 through the valve frametubular portion 32 from the upstream end to the downstream end. Valveframe tubular portion 32 circumscribes axis ax1, and thereby defineslumen 38 along the axis. Valve frame 30 further includes an upstreamsupport portion 40, extending from upstream end 34 of valve frametubular portion 32. Frame assembly 22 further includes at least one leg50 (alternatively, “ventricular anchor support 50”), coupled to valveframe 30 at (e.g., via) a coupling point 52, and having atissue-engaging flange 54 (alternatively, “ventricular anchoring leg54”).

In some embodiments, and as described hereinbelow, ventricular anchorsupport 50 is part of an outer frame 60, and frames 30 and 60 definerespective coupling elements 31 and 61, which are fixed with respect toeach other at coupling points 52. In some embodiments, frames 30 and 60are coupled to each other only at coupling points 52 (e.g., only via thefixation of coupling elements 31 and 61 with respect to each other).

Prosthetic valve 20 further includes a valve member 58 (e.g., one ormore prosthetic leaflets) disposed within lumen 38, and configured tofacilitate one-way liquid flow through the lumen from upstream end 34 todownstream end 36 (e.g., thereby defining the orientation of theupstream and downstream ends of valve frame tubular portion 32). FIG. 1Ashows prosthetic valve 20 in a fully-expanded state, in which frameassembly 22 is in a fully-expanded state. FIG. 1B shows an exploded viewof frame assembly 22 in its fully-expanded state. FIGS. 2A-E showrespective states of prosthetic valve 20, which will be discussed inmore detail hereinbelow with respect to the implantation of theprosthetic valve and the anatomy in which the prosthetic valve isimplanted. FIG. 2A shows prosthetic valve 20 in a compressed state inwhich frame assembly 22 is in a compressed state for percutaneousdelivery of the prosthetic valve to the heart of the subject. Asillustrated in FIGS. 4A and 4B, frame assembly 22 may be in thecompressed state when it is constrained within delivery capsule 90during delivery of the prosthetic valve to the heart; thus, thecompressed state of frame assembly 22 illustrated in FIG. 2A may alsoconstitute a delivery configuration of the frame assembly 22. In someembodiments, in the compressed state, ventricular anchor support 50(including ventricular anchoring leg 54 thereof) is in a constrained-legstate in which the ventricular anchoring leg is generally parallel withaxis ax1. For example, ventricular anchor support 50 (includingventricular anchoring leg 54) may be in the compressed state whenradially constrained within delivery capsule 90, as illustrated in FIG.4A. Further in some embodiments, in the compressed state, upstreamsupport portion 40 (including atrial anchoring arms 46) is generallytubular, collinear with valve frame tubular portion 32 (e.g., extendingcollinearly from the valve frame tubular portion), and disposed aroundaxis ax1. For example, upstream support portion 40 may be in thecompressed state when radially constrained within delivery capsule 90,as illustrated in FIG. 4A.

FIG. 2B shows a state of prosthetic valve 20 in which ventricularanchoring leg 54 of each ventricular anchor support 50, includingterminal leg end 54 a, extends radially away from axis ax1 (e.g.,radially away from valve frame tubular portion 32) in a released-legstate. FIG. 2C shows a state of prosthetic valve 20 in whichupstream-support portion 40 (including atrial anchoring arms 46 andterminal arm ends 46 a thereof) extends radially away from axis ax1 (andthereby radially away from valve frame tubular portion 32) in areleased-arm state. FIG. 2D shows a state of prosthetic valve 20 inwhich both ventricular anchoring leg 54 and portion 40 extend away fromaxis ax1 in their respective released states. In the fully-expandedstate (FIGS. 1A-B, 2E) both upstream support portion 40 and ventricularanchoring leg 54 extend radially away from axis ax1. In someembodiments, frame assembly 22 is biased (e.g., shape-set) to assume itsfully-expanded state, which is shown in FIG. 2E. Transitioning ofprosthetic valve 20 between the respective states may be controlled by adelivery apparatus, such as by constraining the prosthetic valve in acompressed state within a delivery tube and/or against a control rod,and selectively releasing portions of the prosthetic valve to allow themto expand.

In the compressed state of frame assembly 22, valve frame tubularportion 32 has a diameter d1, and in the expanded state, the valve frametubular portion has a diameter d2 that is greater that diameter d1. Forsome embodiments, diameter d1 is 4-15 mm, (e.g., 5-11 mm) and diameterd2 is 20-50 mm, (e.g., 23-33 mm). Frame assembly 22 is configured suchthat increasing the diameter of valve frame tubular portion 32 (e.g.,from d1 to d2) causes longitudinal movement of ventricular anchoring leg54 away from coupling point 52. In the same way, reducing the diameterof valve frame tubular portion 32 (e.g., from d2 to d1) causeslongitudinal movement of ventricular anchoring leg 54 toward couplingpoint 52. It is to be noted that the term “longitudinal movement”(including the specification and the claims) means movement parallelwith central longitudinal axis ax1. Therefore, longitudinal movement ofventricular anchoring leg 54 away from coupling point 52 meansincreasing a distance, measured parallel with longitudinal axis ax1,between ventricular anchoring leg 54 and coupling point 52. An exampleof such a configuration is described in more detail with respect to FIG.3A.

Thus, expansion of valve frame tubular portion 32 from its compressedstate toward its expanded state increases a circumferential distancebetween each of coupling points 52 and its adjacent coupling points(e.g., between each of outer-frame coupling elements 61 and its adjacentouter-frame coupling elements) (e.g., from d8 to d9), and movesventricular anchor supports 50 in a longitudinally upstream directionwith respect to the valve frame tubular portion 32.

In some embodiments, frame assembly 22 is configured such thatincreasing the diameter of valve frame tubular portion 32 also causeslongitudinal movement of upstream support portion 40 toward couplingpoint 52, e.g., as described in more detail with respect to FIGS. 3B-C.In some embodiments, frame assembly 22 is configured such thatincreasing the diameter of valve frame tubular portion 32 also causeslongitudinal movement of upstream end 34 of valve frame tubular portion32 toward coupling point 52. In the same way, reducing the diameter ofvalve frame tubular portion 32 causes longitudinal movement of upstreamend 34 away from coupling point 52.

For some embodiments, upstream support portion 40 includes a pluralityof atrial anchoring arms 46 that each extends radially outward fromvalve frame tubular portion 32 (e.g., from upstream end 34 of the valveframe tubular portion). Atrial-anchoring arms 46 may be flexible. Forsome such embodiments, atrial anchoring arms 46 are coupled to valveframe tubular portion 32 such that each atrial anchoring arm 46 maydeflect independently of adjacent atrial anchoring arms 46 duringimplantation (e.g., due to anatomical topography).

For some embodiments, upstream support portion 40 includes a pluralityof barbs 48 that extend out of a downstream surface of the upstreamsupport portion. For example, each atrial anchoring arm 46 may includeone or more of barbs 48. Barbs 48 press into tissue upstream of thenative valve (e.g., into the valve annulus), thereby inhibitingdownstream movement of prosthetic valve 20 (in addition to inhibition ofdownstream movement provided by the geometry of upstream support portion40).

One or more surfaces of frame assembly 22 are covered with a covering23, which may include a flexible sheet, such as a fabric, e.g.,including polyester. In some embodiments, covering 23 covers at leastpart of valve frame tubular portion 32, in some embodiments lining aninner surface of the valve frame tubular portion, and thereby defininglumen 38.

Further in some embodiments, upstream support portion 40 is covered withcovering 23, e.g., extending between atrial anchoring arms 46 to form anannular shape. It is hypothesized that this reduces a likelihood ofparavalvular leakage. For such embodiments, excess covering 23 may beprovided between atrial anchoring arms 46 of upstream support portion40, so as to facilitate their independent movement. Although FIG. 1Ashows covering 23 covering an upstream side of upstream support portion40, the covering may additionally or alternatively cover the downstreamside of the upstream support portion. For example, covering 23 mayextend over the tips of atrial anchoring arms 46 and down the outside ofthe atrial anchoring arms 46, or a separate piece of covering may beprovided on the downstream side of the upstream support portion.

Alternatively, each atrial anchoring arm 46 may be individually coveredin a sleeve of covering 23, thereby facilitating independent movement ofthe atrial anchoring arms 46.

For some embodiments, at least part of ventricular anchor supports 50(e.g., ventricular anchoring legs thereof) is covered with covering 23.

In some embodiments, frame assembly 22 includes a plurality ofventricular anchor supports 50 (e.g., two or more supports, e.g., 2-16supports, such as 4-12 supports, such as 6-12 supports), arrangedcircumferentially around valve frame 30 (e.g., around the outside ofvalve frame tubular portion 32). In some embodiments, frame assembly 22includes a plurality of coupling points 52 at which the ventricularanchor supports 50 are coupled to valve frame 30.

As described in more detail hereinbelow (e.g., with reference to FIG.3A), each ventricular anchor support 50 may be coupled to a couplingpoint 52 via a strut 70. For some embodiments, each ventricular anchorsupport 50 is coupled to a plurality of (e.g., two) coupling points 52via a respective plurality of (e.g., two) struts 70. For some suchembodiments, frame assembly 22 is arranged such that, in the expandedstate of the frame assembly, ventricular anchor support 50 is disposed,circumferentially with respect to valve frame tubular portion 32,between two struts, and each of the two struts are disposed,circumferentially with respect to the valve frame tubular portion 32,between the ventricular anchor support and a respective coupling point52.

For some embodiments, a plurality of (e.g., two) ventricular anchorsupports are coupled to each coupling point 52 via a respectiveplurality of (e.g., two) struts 70. For some such embodiments, frameassembly 22 is arranged such that, in the expanded state of the frameassembly, coupling point 52 is disposed, circumferentially with respectto valve frame tubular portion 32, between two struts 70, and each ofthe two struts are disposed, circumferentially with respect to the valveframe tubular portion 32, between the coupling point and a respectiveventricular anchor support 50.

For some embodiments, frame assembly 22 includes an outer frame 60 thatcircumscribes valve frame tubular portion 32, includes (or defines) theplurality of ventricular anchor supports 50 and the plurality of struts70, and is coupled to valve frame 30 at the plurality of coupling points52, such that the plurality of ventricular anchor supports 50 aredistributed circumferentially around the valve frame tubular portion 32.For such embodiments, outer frame 60 includes a ring 66 that is definedby a pattern of alternating peaks 64 and troughs 62, and that in someembodiments circumscribes valve frame tubular portion 32. For example,the ring may include struts 70, extending between the peaks and troughs.Peaks 64 are longitudinally closer to upstream end 34 of valve frametubular portion 32 than to downstream end 36, and troughs 62 arelongitudinally closer to the downstream end than to the upstream end.(It is to be noted that throughout this disclosure, including thespecification and the claims, the term “longitudinally” means withrespect to longitudinal axis ax1. For example, “longitudinally closer”means closer along axis ax1 (whether positioned on axis ax1 or lateralto axis ax1), and “longitudinal movement” means a change in positionalong axis ax1 (which may be in additional to movement toward or awayfrom axis ax1).) Therefore, peaks 64 are closer than troughs 62 toupstream end 34, and troughs 62 are closer than peaks 64 to downstreamend 36. As illustrated in FIG. 1B, outer frame 60 may include multiplerings 66; in embodiments depicted in FIG. 1B, outer frame 60 includestwo rings 66 connected by ventricular anchor supports 50. Rings 66 andventricular anchor supports 50 may form an annular outer frame tubularportion 65. Outer frame tubular portion 65 may have an upstream end 67and a downstream end 69, and may circumscribe axis ax1. In someembodiments, upstream end 67 may constitute a portion of the mostupstream ring 66 and downstream end 69 may constitute a portion of themost downstream ring 66. As also illustrated in FIG. 1B, ventricularanchoring legs 54 may extend from outer frame tubular portion 65. Forembodiments in which frame 60 includes ring 66, each ventricular anchorsupport 50 is coupled to the ring (or defined by frame 60) at arespective trough 62.

In the embodiment shown, the peaks and troughs are defined by ring 66having a generally zig-zag shape. However, the scope of the disclosureincludes ring 66 having another shape that defines peaks and troughs,such as a serpentine or sinusoid shape.

In some embodiments, valve frame tubular portion 32 and outer frametubular portion 65 may form annular valve body 25. Annular valve body 25may circumscribe axis ax1. As illustrated in FIGS. 1A and 1B, annularvalve body 25 may include ventricular anchor supports 50, and upstreamsupport portion 40 (including atrial anchoring arms 46) and ventricularanchoring legs 54 may extend from annular valve body 25.

For embodiments in which frame assembly 22 has a plurality of couplingpoints 52, the coupling points (and therefore coupling elements 31 and61) are disposed circumferentially around the frame assembly (e.g.,around axis ax1), in some embodiments on a transverse plane that isorthogonal to axis ax1. This transverse plane is illustrated by theposition of section A-A in FIG. 2B. Alternatively, coupling points 52may be disposed at different longitudinal heights of frame assembly 22,e.g., such that different ventricular anchoring legs 54 are positionedand/or moved differently to others. In some embodiments, coupling points52 (and therefore coupling elements 31 and 61) are disposedlongitudinally between upstream end 24 and downstream end 26 of frameassembly 22, but not at either of these ends. Further in someembodiments, coupling points 52 are disposed longitudinally betweenupstream end 34 and downstream end 36 of valve frame tubular portion 32,but not at either of these ends. For example, the coupling points may bemore than 3 mm (e.g., 4-10 mm) both from end 34 and from end 36. It ishypothesized that this advantageously positions the coupling points at apart of valve frame tubular portion 32 that is more rigid than end 34 orend 36.

It is to be noted that ventricular anchor support 50 may be expandableinto its expanded state (e.g., a released-leg state) such thatventricular anchoring leg 54 extends away from axis ax1, independentlyof increasing the diameter of valve frame tubular portion 32 (e.g., asshown in FIGS. 2B & 2D). Similarly, upstream support portion 40 may beexpandable into its expanded state (e.g., a released-arm state) suchthat it (e.g., atrial anchoring arms 46 thereof) extends away from axisax1, independently of increasing the diameter of valve frame tubularportion 32 (e.g., as shown in FIGS. 2C & 2D). The state shown in FIG. 2Dmay be considered to be an intermediate state. Therefore, prostheticvalve 20 may be configured such that ventricular anchor supports 50(e.g., ventricular anchoring legs 54 thereof) and upstream supportportion 40 are expandable such that they both extend away from axis ax1,while retaining a distance d3 therebetween. This distance issubsequently reducible to a distance d4 by expanding valve frame tubularportion 32 (e.g., shown in FIG. 2E).

For some embodiments, while valve frame tubular portion 32 remains inits compressed state, ventricular anchoring leg 54 can extend away fromaxis ax1 over 40 percent (e.g., 40-80 percent, such as 40-70 percent) ofthe distance that it extends from the axis subsequent to the expansionof the valve frame tubular portion. For example, for embodiments inwhich prosthetic valve 20 includes a ventricular anchoring leg 54 onopposing sides of the prosthetic valve 20, a span d15 of the ventricularanchoring legs 54 while valve frame tubular portion 32 is in itscompressed state may be at least 40 percent (e.g., 40-80 percent, suchas 40-70 percent) as great as a span d16 of the ventricular anchoringlegs 54 subsequent to the expansion of the valve frame tubular portion32. As illustrated in FIGS. 2D and 2E, the term “span” may refer to thediameter of a circle formed by particular features. For example, thespan d15, d16 of the ventricular anchoring legs 54 may refer to thediameter of a circle formed by the terminal leg ends 54 a. Similarly,the span d17, d18 of the upstream support portion 40 may refer to thediameter of a circle formed by the terminal arm ends 46 a. For someembodiments, span d15 is greater than 15 mm and/or less than 50 mm(e.g., 20-30 mm). For some embodiments, span d16 is greater than 30 mmand/or less than 60 mm (e.g., 40-50 mm). It is to be noted thatventricular anchoring leg 54 is effectively fully expanded, with respectto other portions of ventricular anchor support 50 and/or with respectto valve frame tubular portion 32, before and after the expansion of thevalve frame tubular portion 32.

Similarly, for some embodiments, while valve frame tubular portion 32remains in its compressed state, upstream support portion 40 (e.g.,atrial anchoring arms 46) can extend away from axis ax1 over 30 percent(e.g., 30-70 percent) of the distance that it extends from the axissubsequent to the expansion of the valve frame tubular portion. That is,for some embodiments, a span d17 of the upstream support portion 40while valve frame tubular portion 32 is in its compressed state may beat least 30 percent (e.g., 30-70 percent) as great as a span d18 of theupstream support portion subsequent to the expansion of the valve frametubular portion. For some embodiments, span d17 is greater than 16 mm(e.g., greater than 20 mm) and/or less than 50 mm (e.g., 30-40 mm). Forsome embodiments, span d18 is greater than 40 mm and/or less than 65 mm(e.g., 45-56 mm, such as 45-50 mm). It is to be noted that upstreamsupport portion 40 is effectively fully expanded, with respect to valveframe tubular portion 32, before and after the expansion of the valveframe tubular portion 32.

It is to be noted that when valve frame tubular portion 32 is expanded,ventricular anchoring legs 54 may translate radially outward from spand15 to span d16 (e.g., without deflecting). In some embodiments upstreamsupport portion 40 behaves similarly (e.g., atrial anchoring arms 46translated radially outward from span d17 to span d18, e.g., withoutdeflecting). That is, an orientation of each ventricular anchoring leg54 and/or each atrial anchoring arm 46 with respect to valve frametubular portion 32 and/or axis ax1 is in some embodiments the same inthe state shown in FIG. 2D as it is in the state shown in FIG. 2E.Similarly, in some embodiments an orientation of each ventricularanchoring leg 54 with respect to upstream support portion 40 (e.g., withrespect to one or more atrial anchoring arms 46 thereof) is the samebefore and after expansion of valve frame tubular portion 32.

For some embodiments, increasing the diameter of valve frame tubularportion 32 from d1 to d2 causes greater than 1 mm and/or less than 20 mm(e.g., 1-20 mm, such as 1-10 mm or 5-20 mm) of longitudinal movement ofventricular anchoring leg 54 away from coupling point 52. For someembodiments, increasing the diameter of valve frame tubular portion 32from d1 to d2 causes greater than 1 mm and/or less than 20 mm (e.g.,1-20 mm, such as 1-10 mm or 5-20 mm) of longitudinal movement ofupstream support portion 40 toward coupling point 52. For someembodiments, distance d3 is 7-30 mm. For some embodiments, distance d4is 0-15 mm (e.g., 2-15 mm). For some embodiments, increasing thediameter of valve frame tubular portion 32 from d1 to d2 reduces thedistance between the upstream support portion and ventricular anchoringlegs 54 by more than 5 mm and/or less than 30 mm, such as 5-30 mm (e.g.,10-30 mm, such as 10-20 mm or 20-30 mm). For some embodiments, thedifference between d3 and d4 is generally equal to the differencebetween d1 and d2. For some embodiments, the difference between d3 andd4 is more than 1.2 and/or less than 3 times (e.g., 1.5-2.5 times, suchas about 2 times) greater than the difference between d1 and d2.

For some embodiments, ventricular anchoring legs 54 curve such that atip of each ventricular anchoring leg 54 is disposed at a shallowerangle with respect to inner region 42 of upstream support portion 40,than are portions of ventricular anchor support 50 that are closer todownstream end 26 of frame assembly 22. For some such embodiments, a tipof each ventricular anchoring leg 54 may be generally parallel withinner region 42. For some such embodiments, while valve frame tubularportion 32 is in its expanded state, a tip portion 55 of eachventricular anchoring leg 54 that extends from the tip of theventricular anchoring leg at least 2 mm along the ventricular anchoringleg, is disposed within 2 mm of upstream support portion 40. Thus, forsome embodiments, while valve frame tubular portion 32 is in itsexpanded state, for at least 5 percent (e.g., 5-8 percent, or at least 8percent) of span 18 of upstream support portion 40, the upstream supportportion is disposed within 2 mm of a ventricular anchoring leg 54.

For some embodiments, in the absence of any obstruction (such as tissueof the valve or covering 23) between ventricular anchoring leg 54 andupstream support portion 40, increasing the diameter of valve frametubular portion 32 from d1 to d2 causes the ventricular anchoring leg 54and the upstream support portion to move past each other (e.g., theventricular anchoring leg 54 may move between atrial anchoring arms 46of the upstream support portion), such that the ventricular anchoringleg 54 is closer to the upstream end of prosthetic valve 20 than is theupstream support portion, e.g., as shown hereinbelow for frameassemblies 122 and 222, mutatis mutandis. (For embodiments in whichupstream support portion 40 is covered by covering 23, ventricularanchoring legs 54 may not pass the covering. For example, in the absenceof any obstruction, ventricular anchoring legs 54 may pass betweenatrial anchoring arms 46, and press directly against covering 23.) It ishypothesized that in some embodiments this configuration applies greaterforce to the valve tissue being sandwiched, and thereby furtherfacilitates anchoring of the prosthetic valve. That is, for someembodiments, distance d3 is smaller than the sum of distance d5 and adistance d14 (described with reference to FIG. 3C). For someembodiments, increasing the diameter of valve frame tubular portion 32from d1 to d2 advantageously causes ventricular anchoring legs 54 andupstream support portion 40 to move greater than 3 mm and/or less than25 mm (e.g., greater than 5 mm and/or less than 15 mm, e.g., 5-10 mm,such as about 7 mm) with respect to each other (e.g., toward each otherand then past each other).

For some embodiments, in the expanded state of frame assembly 22,upstream support portion 40 has an inner region (e.g., an inner ring) 42that extends radially outward at a first angle with respect to axis ax1(and in some embodiments with respect to valve frame tubular portion32), and an outer region (e.g., an outer ring) 44 that extends, from theinner region, further radially outward from the valve frame tubularportion at a second angle with respect to the valve frame tubularportion, the second angle being smaller than the first angle. Forexample, in some embodiments inner region 42 extends radially outward atan angle alpha_1 of 60-120 degrees (e.g., 70-110 degrees) with respectto axis ax1, and outer region 44 extends radially outward at an anglealpha_2 of 5-70 degrees (e.g., 10-60 degrees) with respect to axis ax1.

It is to be noted that angles alpha_1 and alpha_2 are measured betweenthe respective region support portion 40, and the portion of axis ax1that extends in an upstream direction from the level of frame assembly22 at which the respective region begins to extend radially outward.

In some embodiments in which prosthetic valve 20 is configured to beplaced at an atrioventricular valve (e.g., a mitral valve or a tricuspidvalve) of the subject, region 42 is configured to be placed against theupstream surface of the annulus of the atrioventricular valve, andregion 44 is configured to be placed against the walls of the atriumupstream of the valve.

For some embodiments, outer region 44 is more flexible than inner region42. For example, and as shown, each atrial anchoring arm 46 may have adifferent structure in region 44 than in region 42. It is hypothesizedthat the relative rigidity of region 42 provides resistance againstventricular migration of prosthetic valve 20, while the relativeflexibility of region 44 facilitates conformation of upstream supportportion 40 to the atrial anatomy.

For some embodiments, two or more of atrial anchoring arms 46 areconnected by a connector (not shown), reducing the flexibility, and/orthe independence of movement of the connected atrial anchoring armsrelative to each other. For some embodiments, atrial anchoring arms 46are connected in particular sectors of upstream support portion 40,thereby making these sectors more rigid than sectors in which the atrialanchoring arms 46 are not connected. For example, a relatively rigidsector may be provided to be placed against the posterior portion of themitral annulus, and a relatively flexible sector may be provided to beplaced against the anterior side of the mitral annulus, so as to reduceforces applied by upstream support portion 40 on the aortic sinus.

For some embodiments, and as shown, coupling points 52 are disposedcloser to downstream end 26 of frame assembly 22 than are ventricularanchoring legs 54, or is upstream support portion 40.

As described in more detail with respect to FIGS. 4A-F, the movement ofventricular anchoring leg 54 away from coupling point 52 (and movementof upstream support portion 40 toward the coupling point) facilitatesthe sandwiching of tissue of the native valve (e.g., leaflet and/orannulus tissue) between the ventricular anchoring leg 54 and theupstream support portion, thereby securing prosthetic valve 20 at thenative valve.

In some embodiments, in the compressed state of valve frame tubularportion 32, a downstream end of each ventricular anchor support 50 islongitudinally closer than valve-frame coupling elements 31 todownstream end 36, and ventricular anchoring leg 54 of each ventricularanchor support 50 is disposed longitudinally closer than the valve-framecoupling elements to upstream end 34. In some embodiments, this is alsothe case in the expanded state of valve frame tubular portion 32.

FIGS. 3A-C show structural changes in frame assembly 22 duringtransitioning of the assembly between its compressed and expandedstates, in accordance with some embodiments of the disclosure. FIGS.3A-C each show a portion of the frame assembly, the structural changesthereof being representative of the structural changes that occur inother portions of the frame assembly. FIG. 3A shows a ventricular anchorsupport 50 and struts 70 (e.g., a portion of outer frame 60), andillustrates the structural changes that occur around outer frame 60.FIG. 3B shows a portion of valve frame 30, and illustrates thestructural changes that occur around the valve frame. FIG. 3C showsvalve frame 30 as a whole. In each of FIGS. 3A-C, state (A) illustratesthe structure while frame assembly 22 (and in particular valve frametubular portion 32) is in its compressed state, and state (B)illustrates the structure while the frame assembly (and in particularvalve frame tubular portion 32) is in its expanded state.

FIG. 3A shows structural changes in the coupling of ventricular anchorsupports 50 to coupling point 52 (e.g., structural changes of outerframe 60) during the transitioning of frame assembly 22 (and inparticular valve frame tubular portion 32) between its compressed andexpanded states. Each ventricular anchor support 50 is coupled to valveframe 30 via at least one strut 70, which connects the ventricularanchor support 50 to coupling point 52. In some embodiments, eachventricular anchor support 50 is coupled to valve frame 30 via aplurality of struts 70. A first end 72 of each strut 70 is coupled toventricular anchor support 50, and a second end 74 of each strut iscoupled to a coupling point 52. As described hereinabove, forembodiments in which frame 60 includes ring 66, each ventricular anchorsupport 50 is coupled to the ring at a respective trough 62. Ring 66 mayinclude struts 70, extending between the peaks and troughs, with eachfirst end 72 at (or close to) a trough 62, and each second end 74 at (orclose to) a peak 64.

In the compressed state of frame assembly 22 (and in particular of valveframe tubular portion 32), each strut 70 is disposed at a first angle inwhich first end 72 is disposed closer than second end 74 to thedownstream end of the frame assembly. Expansion of frame assembly 22(and in particular of valve frame tubular portion 32) toward itsexpanded state causes strut 70 to deflect to a second angle. Thisdeflection moves first end 72 away from the downstream end of frameassembly 22. That is, in the expanded state of frame assembly 22, firstend 72 is further from the downstream end of the frame assembly than itis when the frame assembly is in its compressed state. This movement isshown as a distance d5 between the position of end 72 in state (A) andits position in state (B). This movement causes the above-describedmovement of ventricular anchoring legs 54 away from coupling points 52.As shown, ventricular anchoring legs 54 may move the same distance d5 inresponse to expansion of frame assembly 22.

For embodiments in which outer frame 60 includes ring 66, the pattern ofalternating peaks and troughs may be described as having an amplitudelongitudinally between the peaks and troughs, i.e., measured parallelwith central longitudinal axis ax1 of frame assembly 22, and thetransition between the compressed and expanded states may be describedas follows: In the compressed state of frame assembly 22 (and inparticular of valve frame tubular portion 32), the pattern of ring 66has an amplitude d20. In the expanded state frame assembly 22 (and inparticular of valve frame tubular portion 32), the pattern of ring 66has an amplitude d21 that is lower than amplitude d20. Because it is atpeaks 64 that ring 66 is coupled to valve frame 30 at coupling points52, and it is at troughs 62 that ring 66 is coupled to ventricularanchor supports 50, this reduction in the amplitude of the pattern ofring 66 moves ventricular anchor supports 50 (e.g., ventricularanchoring legs 54 thereof) longitudinally further from the downstreamend of the frame assembly. The magnitude of this longitudinal movement(e.g., the difference between magnitudes d20 and d21) is equal to d5.

In some embodiments, distance d5 is the same distance as the distancethat ventricular anchoring leg 54 moves away from coupling point 52during expansion of the frame assembly. That is, a distance betweenventricular anchoring leg 54 and the portion of ventricular anchorsupport 50 that is coupled to strut 70, in some embodiments remainsconstant during expansion of the frame assembly. For some embodiments,the longitudinal movement of ventricular anchoring leg 54 away fromcoupling point 52 is a translational movement (e.g., a movement thatdoes not include rotation or deflection of the ventricular anchoring leg54).

For some embodiments, a distance d6, measured parallel to axis ax1 offrame assembly 22, between coupling point 52 and first end 72 of strut70 while assembly 22 is in its compressed state, is 3-15 mm. For someembodiments, a distance d7, measured parallel to axis ax1, betweencoupling point 52 and first end 72 of strut 70 while assembly 22 is inits expanded state, is 1-5 mm (e.g., 1-4 mm).

For some embodiments, amplitude d20 is 2-10 mm (e.g., 4-7 mm). For someembodiments, amplitude d21 is 4-9 mm (e.g., 5-7 mm).

For some embodiments, and as shown, in the expanded state, first end 72of strut 70 is disposed closer to the downstream end of frame assembly22 than is coupling point 52. For some embodiments, in the expandedstate, first end 72 of strut 70 is disposed further from the downstreamend of frame assembly 22 than is coupling point 52.

For embodiments in which frame assembly 22 includes a plurality ofventricular anchor supports 50 and a plurality of coupling points 52(e.g., for embodiments in which the frame assembly includes outer frame60) expansion of the frame assembly increases a circumferential distancebetween adjacent coupling points 52, and an increase in acircumferential distance between adjacent ventricular anchor supports50. FIG. 3A shows such an increase in the circumferential distancebetween adjacent coupling points 52, from a circumferential distance d8in the compressed state to a circumferential distance d9 in the expandedstate. For some embodiments, distance d8 is 1-6 mm. For someembodiments, distance d9 is 3-15 mm.

For some embodiments, in addition to being coupled via ring 66 (e.g.,struts 70 thereof) ventricular anchor supports 50 are also connected toeach other via connectors 78. Connectors 78 allow the described movementof ventricular anchor supports 50 during expansion of frame assembly 22,but may stabilize ventricular anchor supports 50 relative to each otherwhile the frame assembly is in its expanded state. For example,connectors 78 may bend and/or deflect during expansion of the frameassembly.

FIGS. 3B-C show structural changes in valve frame 30 during thetransitioning of frame assembly 22 between its compressed and expandedstates. Valve frame tubular portion 32 of valve frame 30 is defined by aplurality of cells 80, which are defined by the repeating pattern of thevalve frame. When frame assembly 22 is expanded from its compressedstate toward its expanded state, cells 80 widen from a width d10 to awidth d11 (measured orthogonal to axis ax1 of the frame assembly), andshorten from a height d12 to a height d13 (measured parallel to axis ax1of the frame assembly). This shortening reduces the overall height(i.e., a longitudinal length between upstream end 34 and downstream end36) of valve frame tubular portion 32 from a height d22 to a height d23,and thereby causes the above-described longitudinal movement of upstreamsupport portion 40 toward coupling points 52 by a distance d14 (shown inFIG. 3C). For some embodiments, and as shown, coupling points 52 aredisposed at the widest part of each cell.

Due to the configurations described herein, the distance by whichventricular anchoring legs 54 move with respect to (e.g., toward, ortoward-and-beyond) upstream support portion 40 (e.g., atrial anchoringarms 46 thereof), may be greater than the reduction in the overallheight of valve frame tubular portion 32 (e.g., more than 20 percentgreater, such as more than 30 percent greater, such as more than 40percent greater). That is, prosthetic valve 20 includes a valve frame 30that includes a valve frame tubular portion 32 that circumscribes alongitudinal axis ax1 of the valve frame so as to define a lumen 38along the axis, the valve frame tubular portion 32 having an upstreamend 34, a downstream end 36, a longitudinal length therebetween, and adiameter (e.g., d1 or d2) transverse to the longitudinal axis; a valvemember 58, coupled to the valve frame tubular portion, disposed withinthe lumen, and arranged to provide unidirectional upstream-to-downstreamflow of blood through the lumen; an upstream support portion 40, coupledto the valve frame tubular portion 32; and an outer frame 60, coupled tothe valve frame tubular portion 32, and including a ventricularanchoring leg 54, wherein the prosthetic valve 20 has a first state(e.g., as shown in FIG. 2D and FIG. 4D) and a second state (e.g., asshown in FIG. 2E and FIG. 4E), in both the first state and the secondstate, the upstream support portion 40 extends radially outward from thevalve frame tubular portion 32, and the ventricular anchoring leg 54extends radially outward from the valve frame tubular portion 32, andthe valve frame tubular portion 32, the upstream support portion 40, andthe outer frame 60 are arranged such that transitioning of theprosthetic valve 20 from the first state toward the second stateincreases the diameter of the valve frame tubular portion 32 by adiameter-increase amount (e.g., the difference between d1 and d2),decreases the length of the valve frame tubular portion 32 by alength-decrease amount (e.g., the difference between d22 and d23), andmoves the ventricular anchoring leg 54 a longitudinal distance withrespect to (e.g., toward or toward-and-beyond) the upstream supportportion (e.g., the difference between d3 and d4), this distance beinggreater than the length-decrease amount.

As shown in the figures, valve frame 30 may be coupled to outer frame 60by coupling between a valve-frame coupling element 31 defined by valveframe 30, and an outer-frame coupling element 61 defined by outer frame60 (e.g., an outer-frame coupling element is coupled to end 74 of eachstrut). In some embodiments, elements 31 and 61 are fixed with respectto each other. Each coupling point 52 may therefore be defined as thepoint at which a valve-frame coupling element and a correspondingouter-frame coupling element 61 are coupled (e.g., are fixed withrespect to each other). For some embodiments, and as shown, elements 31and 61 are eyelets configured to be coupled together by a connector,such as a pin or suture. For some embodiments, elements 31 and 61 aresoldered or welded together.

In some embodiments, and as shown, valve-frame coupling elements 31 aredefined by valve frame tubular portion 32, and are disposedcircumferentially around central longitudinal axis ax1. Outer-framecoupling elements 61 are coupled to ring 66 (or defined by frame 60,such as by ring 66) at respective peaks 64.

As shown (e.g., in FIGS. 2A-E), valve frame 30 (e.g., valve frametubular portion 32 thereof) and outer frame 60 (e.g., ring 66 thereof)are arranged in a close-fitting coaxial arrangement, in both theexpanded and compressed states of frame assembly 22. Ignoring spaces dueto the cellular structure of the frames, a radial gap d19 between valveframe 30 (e.g., valve frame tubular portion 32 thereof) and outer frame60 (e.g., ring 66 thereof) may be less than 2 mm (e.g., less than 1 mm),in both the compressed and expanded states, and during the transitiontherebetween. This is facilitated by the coupling between frames 30 and60, and the behavior, described hereinabove, of frame 60 in response tochanges in the diameter of valve frame tubular portion 32 (e.g., ratherthan solely due to delivery techniques and/or tools). For someembodiments, more than 50 percent (e.g., more than 60 percent) of ring66 is disposed within 2 mm of valve frame tubular portion 32 in both thecompressed and expanded states, and during the transition therebetween.For some embodiments, more than 50 percent (e.g., more than 60 percent)of outer frame 60, except for ventricular anchoring legs 54, is disposedwithin 2 mm of valve frame tubular portion 32 in both the compressed andexpanded states, and during the transition therebetween.

The structural changes to frame assembly 22 (e.g., to outer frame 60thereof) are described hereinabove as they occur during (e.g., as aresult of) expansion of the frame assembly (in particular valve frametubular portion 32 thereof). This is the natural way to describe thesechanges because, as described hereinbelow with respect to FIGS. 4A-6,assembly 22 is in its compressed state during percutaneous delivery tothe implant site, and is subsequently expanded. However, the nature ofprosthetic valve 20 may be further understood by describing structuralchanges that occur during compression of the frame assembly (e.g., atransition from the expanded state in FIG. 2E to the intermediate statein FIG. 2D), in particular valve frame tubular portion 32 thereof(including if valve frame tubular portion 32 were compressed byapplication of compressive force to the valve frame tubular portion 32,and not to outer frame 60 except via the valve frame tubular portionpulling outer frame 60 radially inward). Such descriptions may also berelevant because prosthetic valve 20 may be compressed (i.e., “crimped”)soon before its percutaneous delivery, and therefore these changes mayoccur while prosthetic valve 20 is in the care of the operatingphysician.

For some embodiments, the fixation of peaks 64 to respective sites ofvalve frame tubular portion 32 is such that compression of the valveframe tubular portion 32 from its expanded state toward its compressedstate such that the respective sites of the valve frame tubular portionpull the peaks radially inward via radially-inward tension on couplingpoints 52 reduces a circumferential distance between each of thecoupling points and its adjacent coupling points (e.g., from d9 to d8),and increases the amplitude of the pattern of ring 66 (e.g., from d21 tod20).

For some embodiments, the fixation of outer-frame coupling elements 61to valve-frame coupling elements 31 is such that compression of valveframe tubular portion 32 from its expanded state toward its compressedstate such that the valve-frame coupling elements pull the outer-framecoupling elements radially inward reduces a circumferential distancebetween each of the outer-frame coupling elements and its adjacentouter-frame coupling elements (e.g., from d9 to d8), and increases theamplitude of the pattern of ring 66 (e.g., from d21 to d20).

For some embodiments, the fixation of peaks 64 to the respective sitesof valve frame tubular portion 32 is such that compression of the valveframe tubular portion 32 from its expanded state toward its compressedstate pulls the peaks radially inward via radially-inward pulling of therespective sites of the valve frame tubular portion 32 on the peaks,reduces a circumferential distance between each of coupling points 52and its adjacent coupling points (e.g., from d9 to d8), and increasesthe amplitude of the pattern of ring 66 (e.g., from d21 to d20), withoutincreasing radial gap d19 between valve frame 30 (e.g., valve frametubular portion 32 thereof) and the ring by more than 1.5 mm.

For some embodiments, the fixation of outer-frame coupling elements 61with respect to valve-frame coupling elements 31 is such thatcompression of valve frame tubular portion 32 from its expanded statetoward its compressed state pulls outer-frame coupling elements 61radially inward via radially-inward pulling of valve-frame couplingelements 31 on outer-frame coupling elements 61, reduces acircumferential distance between each of the outer-frame couplingelements 61 and its adjacent outer-frame coupling elements 61 (e.g.,from d9 to d8), and increases the amplitude of the pattern of ring 66(e.g., from d21 to d20), without increasing radial gap d19 between valveframe 30 (e.g., valve frame tubular portion 32 thereof) and the ring bymore than 1.5 mm.

Reference is made to FIGS. 4A-F, which are schematic illustrations ofimplantation of prosthetic valve 20 at a native valve 10 of a heart 4 ofa subject, in accordance with some embodiments of the disclosure. Valve10 is shown as a mitral valve of the subject, disposed between a leftatrium 6 and a left ventricle 8 of the subject. However prosthetic valve20 may be implanted at another heart valve of the subject, mutatismutandis. Similarly, although FIGS. 4A-F show prosthetic valve 20 beingdelivered transseptally via a sheath 88, the prosthetic valve 20 mayalternatively be delivered by any other suitable route, such astransatrially, or transapically.

Prosthetic valve 20 is delivered, in its compressed state, to nativevalve 10 using a delivery tool 89 that is operable from outside thesubject (FIG. 4A). In some embodiments, prosthetic valve 20 is deliveredwithin a delivery capsule 90 of tool 89, which retains the prostheticvalve 20 in its compressed state. A transseptal approach, such as atransfemoral approach, is shown. In some embodiments, prosthetic valve20 is positioned such that at least ventricular anchoring legs 54 aredisposed downstream of the native valve (i.e., within ventricle 8). Atthis stage, frame assembly 22 of prosthetic valve 20 is in thecompressed state, as shown in FIG. 2A.

Subsequently, ventricular anchoring legs 54 are allowed to protruderadially outward, as described hereinabove, e.g., by releasing them fromdelivery capsule 90 (FIG. 4B). For example, and as shown, deliverycapsule 90 may include a distal capsule portion 92 and a proximalcapsule portion 94, and the distal capsule portion may be moved a firstdistance in a first direction (that is, distally with respect toprosthetic valve 20) so as to expose ventricular anchoring legs 54. Thefirst distance may be the distance between the position of distalcapsule portion 92 in FIG. 4A (at which ventricular anchoring legs 54are constrained within distal capsule portion 92) and the position ofdistal capsule portion 92 in FIG. 4B (at which the ventricular anchorlegs 54 are released). At this stage, frame assembly 22 of prostheticvalve 20 is as shown in FIG. 2B. As illustrated in FIG. 4B, annularvalve body 25 remains constrained within distal capsule portion 92 atthis stage.

Subsequently, prosthetic valve 20 is moved upstream towards the atrium6, such that upstream support portion 40, in its compressed state, isdisposed upstream of leaflets 12 (i.e., within atrium 6). For someembodiments, and as illustrated in FIG. 4C, the upstream movement ofprosthetic valve 20 causes ventricular anchoring legs 54 to engage theventricular side of leaflets 12. However, because of the relativelylarge distance d3 provided by prosthetic valve 20 (describedhereinabove), in some embodiments it may not be necessary to move theprosthetic valve so far upstream that ventricular anchoring legs 54tightly engage leaflets 12 and/or pull the leaflets upstream of thevalve annulus. Upstream support portion 40, including atrial anchoringarms 46, is then allowed to expand such that it protrudes radiallyoutward, as described hereinabove, e.g., by releasing it from deliverycapsule 90 (FIG. 4D). For example, and as shown, proximal capsuleportion 94 may be moved a second distance in a second direction (thatis, proximally with respect to prosthetic valve 20) so as to exposeupstream support portion 40, including atrial anchoring arms 46. Thesecond distance may be the distance between the position of proximalcapsule portion 94 in FIG. 4C (at which upstream support portion 40 isconstrained within proximal capsule portion 94) and the position ofproximal capsule portion 94 in FIG. 4D (at which upstream supportportion 40 is released). The second direction (i.e., a proximaldirection from prosthetic valve 20) may be opposite of the firstdirection (i.e., a distal direction from prosthetic valve 20). The firstdirection may be towards ventricle 8 (that is, a ventricular direction)while the second direction may be towards atrium 6 (that is, an atrialdirection). At this stage, frame assembly 22 of prosthetic valve 20 isas shown in FIG. 2D, in which distance d3 exists between upstreamsupport portion 40 and ventricular anchoring legs 54, the ventricularanchoring legs have span d15, the upstream support portion has span d17,and (iv) valve frame tubular portion 32 has diameter d1.

As also illustrated in FIG. 4D, annular valve body 25 may remaincompressed at this stage. In some embodiments, expansion of frameassembly 22 is inhibited by distal capsule portion 92 (e.g., byinhibiting expansion of valve frame tubular portion 32 and outer frametubular portion 65), and/or by another portion of delivery tool 89(e.g., a portion of the delivery tool that is disposed within lumen 38).

Subsequently, prosthetic valve 20 is allowed to expand toward itsexpanded state (i.e. the state depicted in FIG. 2E) due to movement ofdistal capsule portion 92 a third distance in the first direction (thatis, distally with respect to prosthetic valve 20). At this stage, and asalso illustrated in FIG. 4E, prosthetic valve 20 may be released fromthe delivery capsule 90. Frame assembly 22 may be released by thismovement of the distal capsule portion 92 such that annular valve body25 fully radially expands, as illustrated in FIG. 4E. As a result, valveframe tubular portion 32 widens to diameter d2, and the distance betweenupstream support portion 40 and ventricular anchoring legs 54 reduces todistance d4 (FIG. 4E). This sandwiches tissue of valve 10 (in someembodiments including annular tissue and/or leaflets 12) betweenupstream support portion 40 and ventricular anchoring legs 54, therebysecuring prosthetic valve 20 at the valve 10. The third distance may bethe distance between the position of distal capsule portion 92 in FIG.4D (at which annular valve body 25 is constrained within distal capsuleportion 92) and the position of distal capsule portion 92 in FIG. 4E (atwhich the annular valve body 25 is released). FIG. 4F shows deliverycapsule 90 having been removed from the body of the subject, leavingprosthetic valve 20 in place at valve 10.

As explained above, movement of distal capsule portion 92 to theposition of FIG. 4E causes annular valve body 25 to fully-expand. Asillustrated in FIGS. 2A-2E, this may increase the span between theatrial anchoring arms 46 and the span between the ventricular anchoringlegs 54. For example, movement of the distal capsule portion 92 to theposition of FIG. 4E may cause the span of the atrial anchoring arms 46to increase from d17 to d18, and may similarly cause the span ofventricular anchoring legs 54 to increase from d15 to d16.

As described hereinabove, prosthetic valve 20 is configured such thatwhen valve frame tubular portion 32 is expanded, ventricular anchoringlegs 54 and upstream support portion 40 move a relatively large distancetoward each other. This enables distance d3 to be relatively large,while distance d4 is sufficiently small to provide effective anchoring.As also described hereinabove, prosthetic valve 20 is configured suchthat ventricular anchoring legs 54 and upstream support portion 40 canextend radially outward a relatively large distance while valve frametubular portion 32 remains compressed. It is hypothesized that for someembodiments, these configurations (independently and/or together)facilitate effective anchoring of prosthetic valve 20, by facilitatingplacement of a relatively large proportion of valve tissue (e.g.,leaflets 12) between the ventricular anchoring legs 54 and the upstreamsupport portion prior to expanding valve frame tubular portion 32 andsandwiching the valve tissue.

It is further hypothesized that the relatively great radially-outwardextension of ventricular anchoring legs 54 and upstream support portion40 prior to expansion of valve frame tubular portion 32, furtherfacilitates the anchoring/sandwiching step by reducing radially-outwardpushing of the valve tissue (e.g., leaflets 12) during the expansion ofthe valve frame tubular portion 32, and thereby increasing the amount ofvalve tissue that is sandwiched.

It is yet further hypothesized that this configuration of prostheticvalve 20 facilitates identifying correct positioning of the prostheticvalve 20 (i.e., with upstream support portion 40 upstream of leaflets 12and ventricular anchoring legs 54 downstream of the leaflets) prior toexpanding valve frame tubular portion 32 and sandwiching the valvetissue.

As shown in FIG. 1A, for some embodiments, in the expanded state offrame assembly 22, prosthetic valve 20 defines a toroidal space 49between ventricular anchoring legs 54 and upstream support portion 40(e.g., a space that is wider than distance d4). For example, space 49may have a generally triangular cross-section. It is hypothesized thatfor some such embodiments, in addition to sandwiching tissue of thenative valve between upstream support portion 40 and ventricularanchoring legs 54 (e.g., the tips of the ventricular anchoring legs),space 49 advantageously promotes tissue growth therewithin (e.g.,between leaflet tissue and covering 23), which over time further securesprosthetic valve 20 within the native valve.

Reference is now made to FIG. 5, which is a schematic illustration of astep in the implantation of prosthetic valve 20, in accordance with someembodiments of the disclosure. Whereas FIGS. 4A-F show an implantationtechnique in which ventricular anchoring legs 54 are expanded prior toupstream support portion 40, in some embodiments the upstream supportportion 40 is expanded prior to the ventricular anchoring legs 54. FIG.5 shows a step in such an application. In particular, FIG. 5 illustratesmovement of proximal capsule portion 94 a second distance in the seconddirection (that is, towards atrium 6) so as to release upstream supportportion 40 (including atrial anchoring arms 46). As discussed above inreference to FIGS. 4C and 4D, the second distance may be the distancebetween the position of proximal capsule portion 94 at which upstreamsupport portion 40 is constrained and the position of proximal capsuleportion 94 in FIG. 5, at which upstream support portion 40 is released.Distal capsule portion 92 may then be moved a first distance in thefirst direction (i.e., towards ventricle 8) to the position depicted inFIG. 6, at which ventricular anchoring legs 54 may be released. Distalcapsule portion 92 may then be further moved a third distance in thefirst direction so as to release annular valve body 25 (as illustratedin FIG. 4E).

Reference is again made to FIGS. 2A-5. As noted hereinabove, prostheticvalve 20 may be implanted by causing ventricular anchoring legs 54 toradially protrude before causing upstream support portion 40 to radiallyprotrude, or may be implanted by causing the upstream support portion 40to protrude before causing the ventricular anchoring legs 54 toprotrude. For some embodiments, prosthetic valve 20 is therebyconfigured to be deliverable in a downstream direction (e.g.,transseptally, as shown, or transapically) or in an upstream direction(e.g., transapically or via the aortic valve). Thus, for someembodiments, an operating physician may decide which delivery route ispreferable for a given application (e.g., for a given subject, and/orbased on available equipment and/or expertise), and prosthetic valve 20is responsively prepared for the chosen delivery route (e.g., by loadingthe prosthetic valve into an appropriate delivery tool).

It is to be noted that for some embodiments, downstream delivery ofprosthetic valve 20 may be performed by expanding ventricular anchoringlegs 54 first (e.g., as shown in FIGS. 4A-F) or by expanding upstreamsupport portion 40 first (e.g., as shown in FIG. 5). Similarly, in someembodiments upstream delivery of prosthetic valve 20 may be performed byupstream support portion 40 first, or by expanding ventricular anchoringlegs 54 first.

Reference is now made to FIG. 6, which is a schematic illustration ofprosthetic valve 20, in the state and position shown in FIG. 4D, inaccordance with some embodiments of the disclosure. For someembodiments, while prosthetic valve 20 is in the state and positionshown in FIG. 4D, leaflets 12 of valve 10 are able to move, at least inpart in response to beating of the heart. Frame (A) shows leaflets 12during ventricular systole, in which the atrial side 12 a of theleaflets 12 may contact the deployed atrial anchoring arms 46. Frame (B)shows the leaflets during ventricular diastole, in which the ventricularside 12 v of the leaflets 12 may contact the deployed ventricularanchoring legs 54. For some such embodiments, blood is thereby able toflow from atrium 6 to ventricle 8, between leaflets 12 and prostheticvalve 20. It is hypothesized that this advantageously facilitates a morerelaxed implantation procedure, e.g., facilitating retaining ofprosthetic valve 20 in this state and position for a duration of greaterthan 8 minutes. During this time, imaging techniques may be used toverify the position of prosthetic valve 20, and/or positioning ofleaflets 12 between upstream support portion 40 and ventricularanchoring legs 54.

Reference is made to FIGS. 7A-B and 8A-B, which are schematicillustrations of frame assemblies 122 and 222 of respective prostheticvalves, in accordance with some embodiments of the disclosure. Exceptwhere noted otherwise, frame assemblies 122 and 222 may be identical toframe assembly 22, mutatis mutandis. Elements of frame assemblies 122and 222 share the name of corresponding elements of frame assembly 22.Additionally, except where noted otherwise, the prosthetic valves towhich frame assemblies 122 and 222 belong are similar to prostheticvalve 20, mutatis mutandis.

Frame assembly 122 includes a valve frame 130 that includes a valveframe tubular portion 132 and an upstream support portion 140 that mayinclude a plurality of atrial anchoring arms 146, and an outer frame 160that circumscribes the valve frame, and includes a plurality ofventricular anchor supports 150 that each include a ventricularanchoring leg 154. In some embodiments, outer frame 160 includes a ring166 to which ventricular anchor supports 150 are coupled. Ring 166 isdefined by a pattern of alternating peaks and troughs, the peaks beingfixed to frame 130 at respective coupling points 152, e.g., as describedhereinabove for frame assembly 22, mutatis mutandis.

Frame assembly 222 includes a valve frame 230 that includes a valveframe tubular portion 232 and an upstream support portion 240 that mayinclude a plurality of atrial anchoring arms 246, and an outer frame 260that circumscribes the valve frame, and includes a plurality ofventricular anchor supports 250 that each include a ventricularanchoring leg 254. In some embodiments, outer frame 260 includes a ring266 to which ventricular anchor supports 250 are coupled. Ring 266 isdefined by a pattern of alternating peaks and troughs, the peaks beingfixed to frame 230 at respective coupling points 252, e.g., as describedhereinabove for frame assembly 22, mutatis mutandis.

Whereas atrial anchoring arms 46 of frame assembly 22 are shown asextending from upstream end 34 of valve frame tubular portion 32, atrialanchoring arms 146 and 246 of frame assemblies 122 and 222,respectively, extend from sites further downstream. (This difference mayalso be made to frame assembly 22, mutatis mutandis.) Valve frametubular portions 32, 132 and 232 are each defined by a repeating patternof cells that extends around the central longitudinal axis. In someembodiments, and as shown, valve frame tubular portions 32, 132 and 232are each defined by two stacked, tessellating rows of cells. In theexpanded state of each valve frame tubular portion, these cells may benarrower at their upstream and downstream extremities than midwaybetween these extremities. For example, and as shown, the cells may beroughly diamond or astroid in shape. In frame assembly 22, each atrialanchoring arm 46 is attached to and extends from a site 35 that is atthe upstream extremity of cells of the upstream row. In contrast, inframe assemblies 122 and 222, each atrial anchoring arm 146 or 246 isattached to and extends from a site 135 (assembly 122) or 235 (assembly222) that is at the connection between two adjacent cells of theupstream row (alternatively described as being at the upstream extremityof cells of the downstream row).

It is hypothesized by the inventors that this lower position of theatrial anchoring arms 146, 246, while maintaining the length of thelumen of the valve frame tubular portion 132, 232, advantageouslyreduces the distance that the valve frame tubular portion 132, 232(i.e., the downstream end thereof) extends into the ventricle of thesubject, and thereby reduces a likelihood of inhibiting blood flow outof the ventricle through the left ventricular outflow tract. It isfurther hypothesized that this position of the atrial anchoring arms146, 246 reduces radial compression of the valve frame tubular portion132, 232 by movement of the heart, due to greater rigidity of the valveframe tubular portion 132, 232 at sites 135 and 235 (which is supportedby two adjacent cells) than at site 35 (which is supported by only onecell).

As shown, in the expanded state of frame assemblies 22, 122 and 222, theventricular anchor supports (50, 150 and 250, respectively) arecircumferentially staggered with the atrial anchoring arms of theupstream support portion (46, 146 and 246, respectively). This allowsthe ventricular anchor supports to move in an upstream direction betweenthe atrial anchoring arms during expansion of the valve frame tubularportion (32, 132 and 232, respectively), facilitating application ofgreater sandwiching force on tissue of the native valve. The lowerposition of the atrial anchoring arms of assemblies 122 and 222 includescircumferentially shifting the position of the atrial anchoring arms bythe width of half a cell. In order to maintain the circumferentialstaggering of the atrial anchoring arms and ventricular anchor supports,rings 166 and 266 (and thereby ventricular anchor supports 150 and 250)are circumferentially shifted correspondingly. As a result, whereas thepeaks of ring 66 generally align with connections between adjacent cellsof the downstream row of cells of valve frame tubular portion 32 (andare fixed to these sites), the peaks of rings 166 and 266 are generallyaligned midway between these sites (i.e., at spaces of the cellularstructure of the valve frame tubular portion). An appendages 168 (forassembly 122) or 268 (for assembly 222) facilitate fixing of the peakwith respect to the tubular structure.

For assembly 122, appendages 168 are defined by valve frame 130 (e.g.,by valve frame tubular portion 132 thereof) and extend (in a downstreamdirection) to the peaks of ring 166, to which they are fixed. Forexample, each appendage 168 may define a valve-frame coupling element131 that is fixed to a respective outer-frame coupling element 161defined by outer frame 260. In some embodiments, appendages 168 extendfrom sites 135. In some embodiments, appendages 168 are integral withvalve frame tubular portion 132 and/or in-plane with the valve frametubular portion (e.g., are part of its tubular shape).

For assembly 222, appendages 268 are defined by outer frame 260, andextend (e.g., in an upstream direction) from the peaks of ring 266. Insome embodiments, appendages 268 extend to sites 235, to which they arefixed. For example, each appendage 268 may define an outer-framecoupling element 261 that is fixed to a respective valve-frame couplingelement 231 defined by valve frame 230 (e.g., by valve frame tubularportion 232 thereof). In some embodiments, appendages 268 are integralwith outer frame 260 and/or in-plane with adjacent portions of outerframe 260, such as ring 266.

Therefore, frame assembly 122 defines a hub at site 135, and frameassembly 222 defines a hub at site 235. For some embodiments, apparatustherefore includes a plurality of prosthetic valve leaflets; and a frameassembly, including a valve frame tubular portion (132 or 232) definedby a repeating pattern of cells, the valve frame tubular portionextending circumferentially around longitudinal axis ax1 so as to definea longitudinal lumen, the prosthetic valve leaflets coupled to the valveframe and disposed within the lumen; an outer frame (160 or 260),including a plurality of ventricular anchor supports (150 or 250),distributed circumferentially around the valve frame tubular portion,each ventricular anchor support having a ventricular anchoring leg (154or 254); an upstream support portion (140 or 240) that includes aplurality of atrial anchoring arms (146 or 246) that extend radiallyoutward from the valve frame tubular portion; and a plurality ofappendages (168 or 268), each having a first end that defines a couplingelement (161 or 261) via which the valve frame tubular portion iscoupled to the outer frame, and a second end; wherein the frame assemblydefines a plurality of hubs (135 or 235), distributed circumferentiallyaround the longitudinal axis on a plane that is transverse tolongitudinal axis ax1, each hub defined by convergence and connectionof, two adjacent cells of the valve frame tubular portion, an atrialanchoring arm of the plurality of atrial anchoring arms, and anappendage of the plurality of appendages.

Reference is made to FIGS. 9A-C, which are schematic illustrations of aprosthetic valve 320 including a frame assembly 322, in accordance withsome embodiments of the disclosure. Except where noted otherwise, frameassembly 322 is identical to frame assembly 122, and prosthetic valve300 is identical to the prosthetic valve to which frame assembly 122belongs, mutatis mutandis. FIG. 9A is a side-view of prosthetic valve320, and FIG. 9B is an isometric bottom-view of the prosthetic valve.

Frame assembly 122 includes a valve frame 330 that includes a valveframe tubular portion 332 and an upstream support portion 340 that mayinclude a plurality of atrial anchoring arms 346, and an outer frame 360that circumscribes the valve frame, and includes a plurality ofventricular anchor supports 350 that each include a ventricularanchoring leg 354. In some embodiments, outer frame 360 includes a ring366 to which ventricular anchor supports 350 are coupled. Ring 366 isdefined by a pattern of alternating peaks and troughs, the peaks beingfixed to frame 330 at respective coupling points 352, e.g., as describedhereinabove for frame assembly 22 and/or frame assembly 122, mutatismutandis.

Frame assembly 322 includes an annular upstream support portion 340 thathas an inner portion 342 that extends radially outward from the upstreamportion (e.g., the upstream end) of valve frame tubular portion 332.Upstream support portion 340 further includes one or more fabric pockets344 disposed circumferentially around inner portion 342, each pocket ofthe one or more pockets having an opening that faces a downstreamdirection (i.e., generally toward the downstream end of prosthetic valve320). In the figures, upstream support portion 340 has a single toroidalpocket 344 that extends circumferentially around inner portion 342.

In some embodiments, a covering 323 (e.g., similar to covering 23,described hereinabove, mutatis mutandis) is disposed over atrialanchoring arms 346, thereby forming pocket 344. Further in someembodiments, atrial anchoring arms 346 are shaped to form pocket 344from covering 323. For example, and as shown, atrial anchoring arms 346may curve to form a hook-shape.

For some embodiments, portion 340 has a plurality of separate pockets344, e.g., separated at atrial anchoring arms 346. For some suchembodiments, covering 323 is loosely-fitted (e.g., baggy) betweenradially-outward parts of atrial anchoring arms 346, e.g., compared toinner portion 342, in which the covering is more closely-fitted betweenradially-inward parts of the atrial anchoring arms.

FIG. 9C shows prosthetic valve 320 implanted at native valve 10. Pocket344 is in some embodiments shaped and arranged to billow in response toperivalvular flow 302 of blood in an upstream direction. If ventricularsystole forces blood in ventricle 8 between prosthetic valve 320 andnative valve 10, that blood inflates pocket 344 and presses it (e.g.,covering 323 and/or the radially-outward part of atrial anchoring arm346) against tissue of atrium 6 (e.g., against the atrial wall), therebyincreasing sealing responsively. It is hypothesized by the inventorsthat the shape and orientation of pocket 344 (e.g., the hook-shape ofatrial anchoring arms 346) facilitates this pressing radially-outward inresponse to the pocket's receipt of upstream-flowing blood.

Pocket(s) 344 may be used in combination with any of the prostheticvalves described herein, mutatis mutandis.

Reference is again made to FIGS. 1A-9C. It is to be noted that unlessspecifically stated otherwise, the term “radially outward” (e.g., usedto describe upstream support portion 40 and ventricular anchoring legs54) means portions of the element are disposed progressively furtheroutward from a central point (such as longitudinal axis ax1 or valveframe tubular portion 32), but does not necessarily mean disposed at 90degrees with respect to longitudinal axis ax1. For example, ventricularanchoring legs 54 may extend radially outward at 90 degrees with respectto longitudinal axis ax1, but may alternatively extend radially outwardat a shallower angle with respect to the longitudinal axis.

It will be appreciated by persons skilled in the art that the presentdisclosure is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present disclosureincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

1-72. (canceled)
 73. A method of releasing a prosthetic valve from adelivery capsule within a heart, wherein the prosthetic valve isconfigured for deployment within a native mitral valve, the methodcomprising: advancing the delivery capsule with the prosthetic valveretained within the delivery capsule into the heart, wherein thedelivery capsule comprises a distal capsule portion and a proximalcapsule portion; moving the distal capsule portion a first distance inthe heart in a first direction relative to the prosthetic valve torelease ventricular anchoring legs of the prosthetic valve from thedelivery capsule; moving the released ventricular anchoring legs intocontact with the native mitral valve; after contacting the native mitralvalve with the released ventricular anchoring legs, moving the proximalcapsule portion a second distance in the heart in a second directionrelative to the prosthetic valve, the second direction being opposite ofthe first direction, to release atrial anchoring arms of the prostheticvalve from the delivery capsule; and moving the distal capsule portion athird distance in the heart in the first direction relative to theprosthetic valve to release an annular valve body of the prostheticvalve from the delivery capsule.
 74. The method of claim 73, wherein therelease of the annular valve body from the delivery capsule occurs afterthe release of the ventricular anchoring legs and the release of theatrial anchoring arms from the delivery capsule.
 75. The method of claim73, wherein the first direction is a downstream direction and the seconddirection is an upstream direction.
 76. The method of claim 73, whereinthe release of the ventricular anchoring legs from the delivery capsuleoccurs while the distal capsule portion is situated at least partiallywithin a ventricle of the heart, and wherein moving the releasedventricular anchoring legs into contact with the native mitral valvecomprises moving the ventricular anchoring legs in an upstream directionuntil the ventricular anchoring legs contact a ventricular side of thenative mitral valve.
 77. The method of claim 76, wherein the release ofthe atrial anchoring arms from the delivery capsule occurs while theproximal capsule portion is situated at least partially within an atriumof the heart, and wherein the release of the annular valve body from thedelivery capsule occurs while the distal capsule portion is situated atleast partially within the ventricle of the heart.
 78. The method ofclaim 73, wherein the movement of the distal capsule portion the firstdistance in the first direction causes terminal leg ends of theventricular anchoring legs to deflect radially outward relative to theannular valve body, wherein the movement of the proximal capsule portionthe second distance in the second direction causes terminal arm ends ofthe atrial anchoring arms to deflect radially outward relative to theannular valve body, and wherein the movement of the distal capsuleportion the third distance in the first direction reduces a longitudinaldistance between the terminal leg ends and the terminal arm ends. 79.The method of claim 73, wherein the annular valve body remainsconstrained within the distal capsule portion during movement of thedistal capsule portion the first distance in the first direction andduring movement of the proximal capsule portion the second distance inthe second direction.
 80. The method of claim 73, wherein the movementof the distal capsule portion the third distance in the first directionreleases the prosthetic valve from the delivery capsule, the annularvalve body being configured for self-expansion such that the release ofthe prosthetic valve from the delivery capsule anchors the prostheticvalve in the native mitral valve.
 81. A method of releasing a prostheticvalve from a delivery capsule within a heart, the delivery capsulecomprising a distal capsule portion and a proximal capsule portion,wherein the method comprises: advancing the delivery capsule into theheart while the prosthetic valve is held within the delivery capsule ina radially-constrained configuration, the outer diameter of theradially-constrained prosthetic valve being smaller than an innerdiameter of the distal capsule portion and an inner diameter of theproximal capsule portion; moving the distal capsule portion a firstdistance in the heart in a downstream direction to release ventricularanchoring legs of the prosthetic valve from the delivery capsule; movingthe proximal capsule portion a second distance in the heart in anupstream direction to release atrial anchoring arms of the prostheticvalve from the delivery capsule, the downstream direction being oppositeof the upstream direction; and after the release of the ventricularanchoring legs and the release of the atrial anchoring arms from thedelivery capsule, moving the distal capsule portion a third distance inthe heart in the downstream direction to release an annular valve bodyof the prosthetic valve from the delivery capsule.
 82. The method ofclaim 81, wherein an outer diameter of the distal capsule portion isequal to an outer diameter of the proximal capsule portion.
 83. Themethod of claim 81, wherein an upstream opening of the distal capsuleportion and a downstream opening of the proximal capsule portion areconfigured to be held together to enclose the prosthetic valve withinthe delivery capsule.
 84. The method of claim 81, wherein the release ofthe ventricular anchoring legs from the delivery capsule occurs prior tothe release of the atrial anchoring arms from the delivery capsule andwhile the distal capsule portion is situated at least partially within aventricle of the heart, and wherein the release of the atrial anchoringarms from the delivery capsule occurs while the proximal capsule portionis situated at least partially within an atrium of the heart.
 85. Themethod of claim 84, wherein the release of the annular valve body fromthe delivery capsule occurs while the distal capsule portion is situatedat least partially within the ventricle of the heart.
 86. The method ofclaim 81, wherein the annular valve body remains constrained within thedistal capsule portion during the movement of the distal capsule portionthe first distance in the downstream direction and during the movementof the proximal capsule portion the second distance in the upstreamdirection.
 87. The method of claim 86, wherein the movement of thedistal capsule portion the third distance in the downstream directionreleases the prosthetic valve from the delivery capsule, the annularvalve body being configured for self-expansion such that the release ofthe prosthetic valve from the delivery capsule anchors the prostheticvalve in a native mitral valve of the heart.
 88. The method of claim 81,wherein the movement of the distal capsule portion the first distance inthe downstream direction causes terminal leg ends of the ventricularanchoring legs to deflect radially outward relative to the annular valvebody, wherein the movement of the proximal capsule portion the seconddistance in the upstream direction causes terminal arm ends of theatrial anchoring arms to deflect radially outward relative to theannular valve body, and wherein the movement of the distal capsuleportion the third distance in the downstream direction reduces alongitudinal distance between the terminal leg ends and the terminal armends.
 89. A method of releasing a prosthetic valve from a deliverycapsule within a heart, wherein the delivery capsule comprises a distalcapsule portion and a proximal capsule portion, the method comprising:advancing the delivery capsule into the heart while the prosthetic valveis retained between the proximal capsule portion and distal capsuleportion of the delivery capsule, wherein the proximal capsule portionand distal capsule portion are advanced along the same delivery routeinto the heart; moving the distal capsule portion a first distance inthe heart in a downstream direction to release ventricular anchoringlegs of the prosthetic valve from the delivery capsule; moving theproximal capsule portion a second distance in the heart in an upstreamdirection to release atrial anchoring arms of the prosthetic valve fromthe delivery capsule, the downstream direction being opposite of theupstream direction; and moving the distal capsule portion a thirddistance in the heart in the downstream direction to release an annularvalve body of the prosthetic valve from the delivery capsule.
 90. Themethod of claim 89, further comprising: removing the delivery capsulefrom the heart after the release of the annular valve body from thedelivery capsule, wherein the proximal capsule portion and distalcapsule portion are removed from the heart along the same removal route.91. The method of claim 90, wherein removing the delivery capsule fromthe heart comprises: moving the distal capsule portion in an upstreamdirection through the released annular valve body.
 92. The method ofclaim 89, wherein the release of the atrial anchoring arms from thedelivery capsule occurs after the release of the ventricular anchoringlegs from the delivery capsule and before the release of the annularvalve body from the delivery capsule.
 93. The method of claim 89,wherein the release of the ventricular anchoring legs from the deliverycapsule occurs while the distal capsule portion is situated at leastpartially within a ventricle of the heart, wherein the release of theatrial anchoring arms from the delivery capsule occurs while theproximal capsule portion is situated at least partially within an atriumof the heart, and wherein the release of the annular valve body from thedelivery capsule occurs while the distal capsule portion is situated atleast partially within the ventricle of the heart.